Sorafenib and CuB exert synergistic antitumor effects against hepatocellular carcinoma cells via inhibition of STAT3 phosphorylation
| Autor: | Hua Li, Mao-Lin Shi, Tao Zhang, Tai Yang, Cheng Xu, Xiaoli Wang, Yao Zhang, Yudi Bai, Xue Yan, Wei Liu, Dong Li, Jiahui Liu, Ri Zhao, Jin Li |
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| Rok vydání: | 2020 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine Sorafenib Carcinoma Hepatocellular Cell cycle checkpoint Cell Survival Apoptosis Caspase 3 General Biochemistry Genetics and Molecular Biology STAT3 Mice 03 medical and health sciences 0302 clinical medicine Epidermal growth factor synergism Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Viability assay Phosphorylation Research Articles EGF CuB biology Chemistry Liver Neoplasms Drug Synergism Hep G2 Cells hepatocellular carcinoma Cell cycle Xenograft Model Antitumor Assays Triterpenes digestive system diseases 030104 developmental biology 030220 oncology & carcinogenesis Cancer research biology.protein Female Signal Transduction Research Article medicine.drug |
| Zdroj: | FEBS Open Bio |
| ISSN: | 2211-5463 |
| Popis: | The present study reports that the combined use of sorafenib and cucurbitacin B can inhibit cell proliferation and induce cell apoptosis in vitro at the same time as reducing tumor progression in vivo, demonstrating synergistic antitumor effects against hepatocellular carcinoma cells. In addition, combination treatment inhibited epidermal growth factor‐induced signal transducer and activator of transcription‐3 (STAT3) phosphorylation. These findings suggest that inhibition of STAT3 phosphorylation may be involved in the synergistic molecular mechanisms. Sorafenib, the first‐line agent for treatment of advanced hepatocellular carcinoma (HCC), improves median overall survival by approximately 3 months. In the present study, we investigated whether sorafenib combined with cucurbitacin B (CuB), a natural tetracyclic triterpenoid isolated from Cucurbitaceae, exerts enhanced antitumor effects against HCC. Cell viability and colony formation ability were detected by cell‐counting kit‐8 and colony formation assays. Cell cycle and apoptosis were analyzed by flow cytometry. Protein expression was detected by western blotting. HepG2 xenografts in nude mice were used to evaluate in vivo antitumor effects. We report that sorafenib and CuB exhibited synergistic effects on cellular proliferation inhibition and cell apoptosis induction, but not on cell cycle arrest. Furthermore, combination treatment enhanced levels of cleaved caspase 3 and cleaved caspase 9, but suppressed phosphorylation of STAT3. Epidermal growth factor, a potent stimulator of signal transducer and activator of transcription‐3 (STAT3), promoted cell viability and colony formation ability, whereas combination treatment exerted inhibitory effects on epidermal growth factor‐induced STAT3 phosphorylation. Finally, HepG2 xenograft mice cotreated with sorafenib and CuB exhibited reduced tumor progression without notable weight loss. In conclusion, sorafenib and CuB exert synergistic antitumor effects through a pathway that may involve STAT3 phosphorylation, and this may represent a promising therapeutic approach for treatment of HCC. |
| Databáze: | OpenAIRE |
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