Frontiers in Oncology
·
2024
·
IF 3.5
Xincheng Huang,Jun Zeng,Siyuan Ruan,Zhuolin Lei,Jingyuan Zhang,Hong Cao
Background Matrine is an alkaloid extracted from Sophorus beans of the legume family, and it has significant effects and a variety of pharmacological activities. Osteosarcoma(OS) is a common malignant bone tumor that is characterized by high incidence and rapid progression. There have been some preliminary studies on the therapeutic effect of matrine on OS, but the specific mechanism remains unclear. Objective The aim of this study was to investigate the antitumor effect of matrine on HOS cells and the underlying molecular mechanism. Methods The effects of matrine on the proliferation, apoptosis and cell cycle progression of HOS cells were determined by CCK-8 assay, TUNEL assay and flow cytometry in vitro . Wound healing and Transwell invasion assays were used to observe the effect of matrine on the migration and invasion of HOS cells. The mechanism underlying the antitumor effect of matrine on HOS cells was investigated by Western blotting. Results Matrine significantly inhibited HOS cell proliferation, promoted HOS cell apoptosis, and arrested HOS cells in the G1 phase of the cell cycle. Both wound healing and Transwell invasion assays showed that matrine inhibited HOS cell migration and invasion. Western blotting results showed that matrine inhibited the activation of the MAPK/ERK signaling pathway. We found that matrine also downregulated Bcl-2 expression, which may be related to protein synthesis inhibition. Conclusion Matrine can inhibit the proliferation of HOS cells, arrest HOS cells in the G1 phase, and promote HOS cell apoptosis through the MAPK/ERK signaling pathway.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER INVESTIGATION
·
2017
·
IF 2.007
Yan Liu,Hong Li,Jiayue Zhang,Xu Gao
The effects of different doses of potassium iodate (KIO3) on the malignancy of thyroid cancer were investigated. Results showed that the proliferation, migration, and invasion of SW579 thyroid cancer cells were improved by 10−6 M KIO3, which was associated with microRNA(miR)-146a deficit; 10−2 M KIO3 significantly enhanced miR-146a level and suppressed SW579 cell proliferation, migration, and invasion. The diverse effects of KIO3 on SW579 cells were associated with the expression changes in miR-146a targets, Bcl-2, Bax, and caspase-3. Our study concludes that different doses of KIO3 have counteracting effects on the malignancy of thyroid cancer through modulating miR-146a level.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2020
·
IF 1.918
Xiaolin Pu,Hua Jiang,Wei Li,Lin Xu,Lin Wang,Yongqian Shu
Background The coatomer protein complex subunit beta 2 (COPB2) gene is upregulated and promotes cell proliferation in some cancer cells. This study aimed to investigate the role of microRNA (miRNA) targeting by COPB2 gene expression in human lung adenocarcinoma cell lines, including NCI-H1975 cells. Material/Methods COPB2 expression in normal human bronchial epithelial cells and lung adenocarcinoma cells was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. NCI-H1975 human lung adenocarcinoma cells were transfected with short-interfering COPB2 (siCOPB2). Cell apoptosis and cell proliferation were evaluated by flow cytometry and Cell Counting Kit-8 (CCK-8) assays, respectively. The transwell assay evaluated cell migration. Targeting of miR-335-3p by COPB2 was predicted using TargetScan 7.2 and verified using a dual-luciferase reporter assay in NCI-H1975 cells. MiR-335-3p mimics were transfected into NCI-H1975 cells. The further functional analysis included detection of protein expression for cyclin D1, tissue inhibitor matrix metalloproteinase-1 (TIMP-1), matrix metallopeptidase 9 (MMP9), Bcl-2, and Bax, to verify the role of miR-335-3p targeting by COPB2 in lung adenocarcinoma cells. Results COPB2 was upregulated in lung adenocarcinoma cells and was a direct target of miR-335-3p mimics. COPB2 knockdown promoted cell apoptosis, inhibited cell migration and proliferation in NCI-H1975 cells. The effects of COPB2 knockdown on NCI-H1975 cells were increased by miR-335-3p mimics, which also further reduced the expression levels of cyclin D1, MMP9, and Bcl-2 and further increased TIMP-1 and Bax by siCOPB2. Conclusions This study showed that COPB2 was the functional target of miR-335-3p in NCI-H1975 human adenocarcinoma cells.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2022
·
IF 2.586
Xiaoping Wu,Qiujie Pang,Fuxiang Zhi,Xiaohong Mao,Yingbin Hu
The role of long non-coding RNA ACTA2 antisense RNA 1 (LncRNA ACTA2-AS1) in colorectal cancer (CRC) was awaited to be elucidated. Clinical specimen and data on ACTA2-AS1 expression in colon adenocarcinoma (COAD) were collected, followed by in situ hybridization . Transfected CRC cell viability, proliferation, migration, and invasion were determined with Cell Counting Kit-8, colony formation, Scratch, and Transwell assays, respectively. Relative expressions of ACTA2-AS1, PCNA, Bcl-2, MMP-2 and MMP-9 were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot . ACTA2-AS1 expression was downregulated in CRC. Overexpressed ACTA2-AS1 repressed the cell viability, proliferation, migration and invasion, increased cleaved caspase-3 level yet decreased PCNA, Bcl-2, MMP-2 and MMP-9 levels. ACTA2-AS1 silencing, however, did oppositely. Collectively, ACTA2-AS1 inhibits the viability, proliferation, migration and invasion of CRC cells to effectively suppress the progression of CRC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2018
·
IF 5.738
Weitong Sun,Xiaoyan Chen,Chao Xie,Yong Wang,Liteng Lin,Kangshun Zhu,Xintao Shuai
Drug resistance, developed through multiple mechanisms, is a major hindrance to successful chemotherapy of tumor. Combination therapy of chemotherapeutic drugs and siRNA represents an emerging strategy which may improve anticancer effect by synergistic actions. In this study, triblock copolymer of poly(ethylene glycol)-block-poly(l-lysine)-block-poly aspartyl (N-(N′,N′-diisopropylaminoethyl)) (PEG-PLL-PAsp(DIP)) was synthesized for the first time to enable the codelivery of BCL-2 siRNA and DOX. The system is supposed to not only bypass drug efflux but also down-regulate the antiapoptotic gene and consequently confronting against chemoresistance as well. Moreover, the pH responsive ability of the codelivery system can prevent drug leakage during circulation and guarantee swift drug release at tumors. The codelivered siRNA serves to suppress the expression of antiapoptotic BCL-2 and hence sensitize the cancer cells to anticancer drugs and produce improved therapeutic effect. Consequently, the codelivery of BCL-2 siRNA and anticancer drug DOX serves as a promising strategy against drug resistance in chemotherapy.
研究领域:
药学
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肿瘤学
·
生物医学工程
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 19
·4803
·
IF 4.183
Shan Jin,Kuan Shi,Liu Liu,Yu Chen,Guangzhong Yang
Xanthones are important chemical constituents ofGarcinia xanthochymusand varied bioactivities including cytotoxicity. However, their anti-tumor mechanism has remained unknown. Here, we isolated and identified a new xanthone named garciniaxanthone I (1) and five known compounds from the bark ofG. xanthochymus. Their structures were elucidated by NMR analysis and HRESIMS. The anti-proliferation activities of all isolated compounds were evaluated on four human tumor cell lines (HepG2, A549, SGC7901, MCF-7). The results demonstrated that the anti-proliferation activity of xanthone was related to the number and location of prenyl groups. We further found that garciniaxanthone I (GXI) could induce HepG2 apoptosis and enhance the expression of cleaved caspase-8, caspase-9, and caspase-3. GXI could also increase Bax level and concurrently reduce the overexpression of Bcl-2, Bcl-XL, Mcl-1, and surviving in HepG2 cells. Moreover, GXI could inhibit cell migration of HepG2 cells by inhibiting the expressions of MMP-7 and MMP-9. In summary, our study suggests that GXI could induce HepG2 apoptosis via the mitochondrial pathway and might become a lead compound for liver cancer treatment.Keywords:xanthones;Garcinia xanthochymus;apoptosis;HepG2;caspase;Bcl-2 family;MMPs
研究领域:
药理学
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肿瘤学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Oncology Letters
·
2018
·Vol. 15
·期 4
·5739-5743
·
IF 1.664
Hua Zhang,Yumei Cao,Yuru Chen,Guangxi Li,Hanshu Yu
The present study investigated the inhibitory effects of apatinib on the proliferation of the SMMC-7721 hepatocellular carcinoma cell line to explore the possible mechanism. The MTT assay was used to detect the inhibitory effects of the different concentrations of apatinib on the proliferation of SMMC-7721 cells. Annexin V/PI double staining was performed to investigate the effects of apatinib on the apoptosis of SMMC‑7721 cells. Expression of the apoptosis-related genes Bcl-2, Bax and caspase-9 after apatinib treatment was detected by reverse transcription‑quantitative PCR (RT-qPCR) and western blot analysis. Expression of the PI3K, p-PI3K, Akt and p-Akt proteins after apatinib treatment was detected using western blot analysis. The MTT results showed that apatinib inhibited the in vitro proliferation of SMMC-7721 cells. Annexin V/PI double staining showed that apatinib induced the apoptosis of SMMC‑7721 cells in a concentration-dependent manner. Results of RT-qPCR and western blot analysis showed that apatinib was able to induce the expression of pro-apoptotic genes Bax and caspase-9 and inhibited the expression of anti-apoptotic gene Bcl-2. In addition, the western blot analysis revealed that p-PI3K and p-Akt was significantly decreased following apatinib treatment, while no significant differences were found in the total protein levels of PI3K and Akt. The results of the present show that apatinib is capable of promoting the apoptosis of SMMC-7721 cells by inhibiting the PI3K/Akt signal transduction pathway, upregulating the expression of pro-apoptotic genes Bax and caspase-9, and downregulating the expression level of the anti-apoptotic gene Bcl-2.
研究领域:
肿瘤学
·
分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2016
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IF 3.055
Keyou Li,Rui Zhou,Wang Wang Jia,Zhe Li,Jiazhou Li,Pengfei Zhang,Tiancun Xiao
Ethnopharmacological relevance: Zanthoxylum bungeanum ( ZB ), a Chinese herb medicine, has been shown to possess a wide range of biological activities including anti-tumor, anti-inflammatory, and anti-microbial activity and has long been used to treat a variety of skin diseases including psoriasis . However, the underlying mechanism of action has not been systematically elucidated. Aim of the study: to analyze the chemical composition of the hydro-distilled Zanthoxylum bungeanum essential oil (ZBEO), and to investigate its anti-proliferative activity on HaCaT cells as well as the underlying anti-psoriasis mechanisms. Materials and methods: The chemical composition of ZBEO was analyzed with gas chromatography coupled to mass spectrometry (GC-MS). HaCaT cells was exposed to different dose of ZBEO added in medium prior to morphologic features analysis as well as cell cycle arrest examination with Flow cytometry. Western blot analysis was employed to estimate the expression level of proteins including caspase-8/9/3, PARP, Bax and Bcl-2. Results: Thirty-nine compounds of the ZBEO were identified GC-MS. ZBEO-treated HaCaT cells showed typical apoptotic morphologic features by DAPI staining assay. The ZBEO significantly inhibited proliferation of HaCaT cells in a dose- and time-dependent manner and induced S phase arrest apoptosis in HaCaT cells. Furthermore, western blot analysis revealed that the ZBEO increased expression of cleaved caspase-8/9/3, PARP, and Bax, decreased Bcl-2 levels. Conclusion: ZBEO inhibits the proliferation of HaCaT cells, resulting from the induction of cellular apoptosis through both intrinsic and extrinsic pathways. ZBEO is a potential candidate that may be considered for development into an anti-psoriasis drug.
研究领域:
药理学
·
皮肤科
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 19
·期 1
·375-383
·
IF 1.448
Xiaowei Shen,Jiaqi Lei,Lei Du
The limited efficacy of chemotherapy with Taxol (TAX) and cisplatin (DDP) in triple‑negative breast cancer (TNBC) has prompted the investigation of combined therapies. Previous studies demonstrated that microRNA (miR)‑31‑5p is involved in various biological processes. In the present study, it was hypothesized that the overexpression of miR‑31‑5p may enhance the efficacy of chemotherapy. The expression levels of miR‑31‑5p in the TNBC cell lines MDA‑MB‑231 and MDA‑MB‑468 were measured using reverse transcription‑quantitative PCR following transfection with miR‑31‑5p mimic or inhibitor. A Cell Counting Kit‑8 and flow cytometry assays suggested that the overexpression of miR‑31‑5p inhibited cell proliferation and promoted apoptosis, and these effects were reversed by transfecting a miR‑31‑5p inhibitor into MDA‑MB‑231 and MDA‑MB‑468 cells. Furthermore, the overexpression of miR‑31‑5p increased the sensitivity of cells to chemotherapy, which exhibited an increase in apoptosis and in the expression level of Bax, and a decrease in the expression level of Bcl‑2. Chemotherapy resistance induced by miR‑31‑5p inhibitor could be reversed by inhibiting the AKT signaling pathway in MDA‑MB‑231 and MDA‑MB‑468 cells. In conclusion, the present preclinical results indicated that targeting miR‑31‑5p may enhance the efficacy of TAX‑ and DDP‑mediated chemotherapy in TNBC.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2017
·Vol. 22
·期 11
·1814
·
IF 2.861
Wenrui Wang,Lingyu Zhang,Tiantian Chen,Wen Guo,Xunxia Bao,Dandan Wang,Baihui Ren,Haifeng Wang,Yu Li,Yueyue Wang,Sulian Chen,Baoding Tang,Qingling Yang,Changjie Chen
In this study, resveratrol-loaded solid lipid nanoparticles (Res-SLNs) were successfully designed to treat MDA-MB-231 cells. The Res-SLNs were prepared using emulsification and low-temperature solidification method. The Res-SLNs were spherical, with small size, negative charge, and narrow size distribution. Compared with free resveratrol, the Res-SLNs displayed a superior ability in inhibiting the proliferation of MDA-MB-231 cells. In addition, Res-SLNs exhibited much stronger inhibitory effects on the invasion and migration of MDA-MB-231 cells. Western blot analysis revealed that Res-SLNs could promote the ratio of Bax/Bcl-2 but decreased the expression of cyclinD1 and c-Myc. These results indicate that the Res-SLN may have great potential for breast cancer treatment.Keywords:solid lipid nanoparticle;resveratrol;breast cancer;cyclinD1
研究领域:
药理学
·
肿瘤学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2023
·
IF 5.2
Man Ding,Xuechen Zhang,Jiangying Shi,Kaili Cui,Ruipeng Yang,Fengming Liu,Shuhua Shan,Ghani Israr,Zhuoyu Li
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, occurring in the colon or rectum portion. Quinoa is a dicotyledonous plant, and the quinoa bran is the outer seed coat of quinoa. Functional molecules in plants play an important role in the treatment and alleviation of chronic diseases. In this study, quinoa bran was used as the raw material. The active components with an anti-colorectal cancer effect were extracted by acetone and separated with an AB-8 macroporous resin column, which was further identified as terpenoids by liquid-mass spectrometry (LMS), named Quinoa bran terpenoids (QBT). The yield of quinoa bran terpenoids was 0.77%. Moreover, the results showed that QBT significantly inhibited the proliferation of colorectal cancer cells DLD-1 and HCT-8 with a concentration gradient dependent manner. Respectively, the IC 50 values of DLD-1 and HCT-8 cells were 0.42 ± 0.02 and 0.54 ± 0.05 mg/mL. Further studies showed that QBT upregulated apoptosis-related proteins such as activated-caspase-3, 8, and 9. In addition, QBT decreased mitochondrial membrane potential , promoted the expression of the pro-apoptotic protein Bax, and inhibited the anti-apoptotic protein Bcl-2. The experiments showed that QBT significantly repressed the growth of tumors in nude mice . In conclusion, these results indicated that QBT largely inhibits the development of colorectal cancer to large extent through upregulation of caspase-3, 8, and 9 and reduction of mitochondrial membrane potential, and has great potential for anti-tumor progression.
研究领域:
肿瘤学
·
药理学
·
植物科学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Ma Shitang,Zhang Ning,Hou Jiafu,Liu Shijuan,Wang Jiawen,Lu Baowei,Zhu Fucheng,Wei Peipei,Hong Ge,Liu Tianjun
Ligustrazine (TMP) is a natural pyrazine alkaloid extracted from the roots of Ligusticum Chuanxiong Hort, which has the potential as an antitumor agent. A series of 33 ligustrazine–heterocycle (TMPH) derivatives were designed, synthesized, and investigated via antitumor screening assays, molecular docking analysis, and prediction of drug-like properties. TMP was attached to other heterocyclic derivatives by an 8–12 methylene alkyl chain as a linker to obtain 33 TMPH derivatives. The structures were confirmed by 1H-NMR, 13C-NMR, and high-resolution mass spectroscopy spectral (HR-MS) data. The antiproliferative activity against human breast cancer MCF-7, MDA-MB-231, mouse breast cancer 4T1, mouse fibroblast L929, and human umbilical vein endothelial HUVEC cell lines was evaluated by MTT assay. Compound 12–9 displayed significant inhibitory activity with IC50 values in the low micromolar range (0.84 ± 0.02 µM against the MDA-MB-231 cell line). The antitumor effects of compound 12–9 were further evaluated by plate cloning, Hoechst 33 342 staining, and annexin V-FITC/PI staining. The results indicated that compound 12–9 inhibited the proliferation and apoptosis of breast cancer cells. Furthermore, molecular docking of compound 12–9 into the active site of the Bcl-2, CASP-3, and PSMB5 target proteins was performed to explore the probable binding mode. The 33 newly synthesized compounds were predicted to have good drug-like properties in a theoretical study. Overall, these results indicated that compound 12–9 inhibited cell proliferation through PSMB5 and apoptosis through Bcl-2/CASP-3 apoptotic signaling pathways and had good drug-like properties. These results provided more information, and key precursor lead derivatives, in the search for effective bioactive components from Chinese natural medicines.
研究领域:
药理学
·
肿瘤学
·
分子生物学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）