Bioengineering & Translational Medicine
·
2021
·Vol. 7
·期 2
·e10290
·
IF 10.711
Fabiao Hu,Changping Deng,Yiwen Zhou,Yuping Liu,Tong Zhang,Peiwen Zhang,Zhangting Zhao,Hui Miao,Wenyun Zheng,Wenliang Zhang,Meiyan Wang,Xingyuan Ma
Regulation of the apoptotic pathway plays a critical role in inducing tumor cell death and circumventing drug resistance. Survivin protein is the strongest inhibitor of apoptosis found so far. It is highly expressed in several cancers and is a promising target for cancer therapy. However, clinical applications are limited by incomplete inhibition of survivin expression. Here, we present a novel strategy that extended the release of YM155 (an effective survivin inhibitor that works by inhibiting the activity of survivin promoter) and TATm-survivin (T34A) (TmSm) protein (survivin protein mutant with penetrating peptide, a potential anticancer protein therapeutic) via tumor matrix microenvironment-mediated ferritin heavy chain nanocages (FTH1 NCs), enabling significant inhibition of survivin activity at both transcript and protein levels. FTS (FTH1-matrix metalloproteinase-2-TmSm)/YM155 NC synthesis was easily scaled up, and these NCs could sequentially release TmSm protein through matrix metalloproteinase-2 and promote YM155 to enter the nucleus via transferrin receptor 1 (TfR1) binding, which increased the cytotoxicity and apoptosis of Capan-2 and A549 cells compared to that with individual drugs. Moreover, FTS/YM155 NCs enhanced drug accumulation at tumor sites and had a higher tumor inhibition rate (88.86%) than the compounds alone in A549 tumor-bearing mice. In addition, FTS/YM155 NCs exerted significant survivin downregulation (4.43-fold) and caspase-3 upregulation (4.31-fold) and showed better therapeutic outcomes without inducing organ injury, which highlights their promising future clinical application in precision therapy. This tumor microenvironment-responsive platform could be harnessed to develop an effective therapy via multilevel inhibition of cancer targets.
研究领域:
癌症生物学
·
纳米技术
·
药学
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2022
·
IF 4.885
Shiying Zeng,Qinglai Tang,Kang Jiang,Xiaojun Tang
Metformin (MET) and survivin siRNA were delivered using silk fibroin nanoparticles (SFNs) modified with polyethyleneimine (PEI). Nanoparticle functional groups, structural, stability and physicochemical characteristics of the nanoparticles were determined. SFNs loaded with siRNA that had appropriate size, zeta potential , and stability were confirmed by various analytical and spectroscopical methods. The vitro cytotoxicity analysis was performed using CNE2 nasopharyngeal carcinoma cells with different compositions, and the results showed that the newly fabricated nanoparticles effectively triggered apoptosis in CNE2. Afterward, the mice analysis was used to investigate the in vivo therapeutic efficacy. With no apparent weight loss, the co-delivery systems dramatically slowed nasopharyngeal tumor development in mice. Survivin siRNA and MET increased the number of apoptotic tumor cells on histopathology slides. Apoptosis induction in cancer cells and therapeutic effectiveness were satisfactory with the drug delivery method. In this way, it might be used as a therapeutic agent in the fight against nasopharyngeal cancer.
研究领域:
医学
·
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
ONCOLOGY REPORTS
·
2015
·Vol. 34
·期 6
·3147-3155
·
IF 2.301
Lili Zhang,Jie Zhang,Li Chen,Jianli Wang
Autophagy is an intracellular multi-step catabolic degradation process that involves the degradation and recycling of cellular proteins and cytoplasmic damaged organelles to maintain cellular homeostasis and reduction of metabolic stress. Numerous studies have indicated the importance of autophagy in cancer, but the role of autophagy in human skin squamous cell carcinoma (SSCC) development and response to therapy it is still unclear. In the present study, we investigated the role of autophagy in SSCC and the relationship with chemotherapy sensitivity. The present study demonstrated that autophagy related gene the microtubule-associated protein 1 light chain 3 (LC3) expression was low in SSCC. The negative correlation with Bcl2 and survivin, and the chemotherapy drug 5-FU increased the level of autophagy and the autophagy inhibitor 3-MA inhibited this effect in SSCC cells, time- and dose-dependently. When SSCC cells were treated first with 3-MA and then with 5-FU, the inhibition of proliferation, migration, invasion and apoptosis of SSCC cells was enhanced. Our results suggested the possibility of autophagy as a potential target in SSCC therapy and 3-MA and 5-FU combination treatment may be an effective SSCC therapy via autophagy modulating.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2021
·Vol. 22
·期 24
·13314
·
IF 5.924
Feng Guo,Junfeng Ke,Zhengdong Fu,Wenzhao Han,Liping Wang
Cell penetrating peptides (CPPs) are peptides that can directly adapt to cell membranes and then permeate into cells. CPPs are usually covalently linked to the surface of nanocarriers to endow their permeability to the whole system. However, hybrids with lipids or polymers make the metabolism much more sophisticated and even more difficult to determine. In this study, we present a continuous sequence of 18 amino acids (FFAARTMIWY(d-P)GAWYKRI). It forms nanospheres around 170 nm, which increase slightly after loading with siRNA and DOX. Notably, it can be internalized by cancer cells mainly through electronic interactions and PD-L1-mediated endocytosis. Compared with poly-l-lysine and polyethyleneimine, it has a much higher efficiency (about four times) of gene transduction while lowering toxicity. In the treatment of cancer, it causes apoptosis (21%) and inhibits the expression of SURVIVIN protein in vitro. In vivo, it shows good biocompatibility as there are no changes in mice’s body weight. When administering peptide-siRNA-DOX, tumor growth is inhibited the most (about three times). These results above prove the sequence to be a good candidate for gene therapy and drug delivery.Keywords:peptide;self-assembly;gene therapy;PD-L1
研究领域:
癌症治疗
·
纳米技术
·
药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2015
·
IF 3.574
Dongli Li,Zhiyun Du,Chenyue Li,Yue Liu,Susan Goodin,Huarong Huang,Yan He,Yuan Zhang,Huaqian Wang,Xi Zheng,Kun Zhang
Five terpenoids ( 1 – 5 ) from a vegetable plant Acanthopanax trifoliatus (L.) Merr. were investigated for their effects on human prostate cancer cells. The diterpenoid ( 3 ) and triterpenoids ( 4 and 5 ) were found to inhibit the growth and stimulate apoptosis in PC-3 cells. The effects of these terpenoids on PC-3 cells were associated with strong suppression of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3). These terpenoids also inhibited the expression of survivin, a downstream target of NF-κB and STAT3. The in vivo study using a xenograft mouse model showed that 5 strongly inhibited the formation and growth of PC-3 tumours. Moreover, treatment with 5 strongly decreased the expression of phospho-STAT3 and survivin in PC-3 tumours. Our results indicate that 5 has preventive efficacy on the development of PC-3 xenograft tumours. This terpenoid may serve as a candidate for future development as a novel agent for prostate cancer prevention.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
·
IF 9.9
Mengru Cai,Yu Yao,Dongge Yin,Rongyue Zhu,Tingting Fu,Jiahui Kong,Kaixin Wang,Jing Liu,Aina Yao,Yidan Ruan,Wenjuan Shi,Qian Zhu,Jian Ni,Xingbin Yin
In recent years, small interfering RNA (siRNA) has been widely used in the treatment of human diseases, especially tumors, and has shown great appeal. However, the clinical application of siRNA faces several challenges. Insufficient efficacy, poor bioavailability, poor stability, and lack of responsiveness to a single therapy are the main problems affecting tumor therapy. Here, we designed a cell-penetrating peptide (CPP)-modified metal organic framework nanoplatform (named [email protected] @survivin [email protected] , [email protected] ) for targeted co-delivery of oridonin (ORI), a natural anti-tumor active ingredient) and survivin siRNA in vivo. This can improve the stability and bioavailability of siRNA and the efficacy of siRNA monotherapy. The high drug-loading capacity and pH-sensitive properties of zeolite imidazolides endowed the [email protected] with lysosomal escape abilities. The Polyethylene glycol (PEG)-conjugated CPP (PEG-CPP33) coating significantly improved the uptake in the [email protected] in vitro and in vivo. The results showed that the co-delivery of ORI and survivin siRNA greatly enhanced the anti-tumor effect of [email protected] , demonstrating the synergistic effect between ORI and survivin siRNA. In summary, the novel targeted nanobiological platform loaded with ORI and survivin siRNA presented herein showed great advantages in cancer therapy, and provides an attractive strategy for the synergistic application of chemotherapy and gene therapy.
研究领域:
纳米技术
·
药学
·
癌症研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2019
·
IF 3.131
Chuanmin Zhang,Shubiao Zhang,Defu Zhi,Yinan Zhao,Shaohui Cui,Jingnan Cui
This work designed a new delivery system (L-PTX-PSur), which could efficiently co-deliver paclitaxel (PTX) and survivin siRNA (Sur) to overcome the dose-limiting toxicity by effectively accumulating PTX in tumor and obtain enhanced therapy by synergistic effect. In this co-delivery system, protamine was selected to condense siRNA into a compacted ‘core’, and a carbamate-linked cationic lipid was used to develop PTX-loaded liposome to entrap the core. L-PTX-PSur with protamine could facilitate Sur entry into NCI-H460 cells and exhibited high encapsulation efficiency of PTX. In vitro studies on the NCI-H460 lung cancer cells revealed that L-PTX-PSur offered significant advantages over the control groups, and it had the highest cellular uptake, the lowest cell viability and the strongest apoptosis. Western blot result showed that survivin protein expression could be noticeably suppressed by L-PTX-PSur in NCI-H460 cells. And the down-regulation of survivin protein could lower the apoptotic threshold of cancer cells and render PTX more effective with low doses. Collectively, L-PTX-PSur with a low dose of PTX could induce a synergistic inhibitory effect on cancer cells growth by the collaboration of PTX and Sur. This work provides a promising strategy for the treatment of lung cancer.
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Feifei Yang,Wei Huang,Yunfei Li,Shan Liu,Mingji Jin,Yuli Wang,Lihua Jia,Zhonggao Gao
Recently, survivin has been attracting great attention because it plays an important role in inhibiting the apoptosis process of tumor cells. Down-regulating the expression of survivin gene by small interfering RNA (siRNA) offers a promising method for anti-tumor therapy. However, lack of appropriate siRNA delivery vector has significantly hindered the successful application of survivin-targeted siRNA in anti-tumor therapy. The purpose of this study was to use polysaccharide vector TAT-g-CS we synthesized to deliver functional siRNA and evaluate its in vivo anti-tumor activity. TAT-g-CS vector was firstly synthesized and well structurally characterized. MTT assay showed that TAT-g-CS vector exhibited good biocompatibility . TAT-g-CS complexed with siRNA offering nanoparticles with an average particle size of 212.2 nm and a polydispersity index of 0.121, and the zeta potential of the nanoparticles was +18.58 mV. Results from reporter gene assay suggested that luciferase-targeted siRNA when delivered by TAT-g-CS could down-regulate the expression of luciferase gene with 75.3% reduction. Most importantly, we use siRNA Sur targeting survivin gene to assess the in vitro and in vivo delivery capacity of TAT-g-CS and its anti-tumor effects. Our results demonstrated that TAT-g-CS/siRNA Sur nanoparticles not only strongly inhibited the in vitro proliferation of 4T1-Luc tumor cells via inducing cell apoptosis, but also effectively inhibited the in vivo growth and metastasis of malignant breast tumor, which suggested that TAT-g-CS/siRNA nanoparticle was a highly efficient non-viral system for siRNA delivery, especially for anti-tumor therapy based on siRNA therapeutics.
研究领域:
癌症生物学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Translational Cancer Research
·
2019
·
IF 1.07
Heqi Bu,Dianlei Liu,Junhui Cui,Ke Cai,Feng Shen
Background Oridonin has been demonstrated to have anticancer effect on all kinds of cancer cells and it has shown anti-tumor activity in some tumors partially via the inactivation of Wnt/β-catenin signaling pathway. The study investigated the anticancer effect of oridonin on colon carcinoma cell line COLO205 and explored underlying mechanism. Methods Cell Counting Kit-8 (CCK-8) assay was performed to assess cell viability. Flow cytometry was performed to analyze the apoptosis. The key target genes and proteins involved in Wnt/β-catenin pathway were detected by quantitative polymerase chain reaction (qPCR) and Western blotting. The xenograft tumor model of colon cancer COLO205 cell was introduced to detect anti-tumor effects in vivo . Transferase-mediated dUTP nick end labeling (TUNEL) assay was adopted to test the apoptotic cells in the tumor tissues. Results Oridonin inhibited the proliferation of colon cancer COLO205 cells in a dose-dependent and time-dependent manner. Oridonin induced apoptosis by increasing the cleavage of caspases in vitro . Furthermore, the expression levels of β-catenin and its downstream targets, including c-myc, cyclinD1 and survivin were significantly reduced. Nevertheless the knockdown of β-catenin by specific small interfering RNA (siRNA) could augment the anti-proliferative and pro-apoptotic effects by oridonin in COLO205 cells. Meanwhile, oridonin also increased protein expression level of glycogen synthase kinase 3β (GSK3β) and decreased the phosphorylation level of GSK3β. In vivo , oridonin treatment significantly suppressed tumor growth of COLO205 cell xenografts, and which was accompanied by the restrain of Wnt/β-catenin pathway. Conclusions Our present study demonstrated that the growth inhibition and apoptosis induction in colon cancer COLO205 cells by oridonin could be partially mediated through discontinuing Wnt/β-catenin signaling pathway.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）