Haowei Liu,Qiuming Huang,Yunqi Fan,Bo Li,Xuemei Liu,Changhua Hu
Colorectal cancer (CRC) is a type of malignant tumor that seriously threatens human health and life, and its treatment has always been a difficulty and hotspot in research. Herein, this study for the first time reports that antipsychotic aripiprazole (Ari) against the proliferation of CRC cells both in vitro and in vivo , but with less damage in normal colon cells. Mechanistically, the results showed that 5-hydroxytryptamine 2B receptor (HTR2B) and its coupling protein G protein subunit alpha q (G α q) were highly distributed in CRC cells. Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling. Blockade of HTR2B signaling suppressed the growth of CRC cells, but HTR2B was not found to have independent anticancer activity. Interestingly, the binding of G α q to HTR2B was decreased after Ari treatment. Knockdown of G α q not only restricted CRC cell growth, but also directly affected the anti-CRC efficacy of Ari. Moreover, an interaction between Ari and G α q was found in that the mutation at amino acid 190 of G α q reduced the efficacy of Ari. Thus, these results confirm that G α q coupled to HTR2B was a potential target of Ari in mediating CRC proliferation. Collectively, this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.
The prevalence of non-alcoholic fatty liver disease (NAFLD) and related mortality are increasing at an unprecedented rate. Traditional Chinese medicine (TCM) has been shown to offer potential for early prevention and treatment for NAFLD. This study examined the new mechanism of "Shenling Baizhu San" (SLBZS) in the prevention and treatment of NAFLD at the preclinical level.The male C57BL/6J mice were randomly divided into three groups: ND (normal diet), WDC (Western Diet+CCl4 injection) and WDC+SLBZS (SLBZS intervention). Body weight, energy intake, liver enzymes, pro-inflammatory factors and steatosis were recorded in detail. Meanwhile, TPH1, 5-HT, HTR2A and HTR2B were tested by qRT-PCR or ELISA. Dynamic changes in gut microbiota and metabolites were further detected through 16S rRNA gene and untargeted metabolomics.
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