Abstract
Objective:To explore the effect of combined Sorafenib/ cisplatinum treatment on the autophagy and proliferation of hepatocellular carcinoma (HepG2) cells in vitro. Methods:HepG2 cells were cultured and treated with different concentrations of Sorafenib, cisplatinum, or a combination of both over a 24-hour period. Cell proliferation was evaluated using a CCK8 assay, and the mRNA expression of the autophagy-related proteins AKT, mTOR, and LC3 were detected using quantitative PCR (qPCR). AKT, pAKT (Ser473), mTOR, pmTOR (Ser2448), LC3I, and LC3II protein expression levels were evaluated by western blot. Results:We found that the survival rate of HepG2 cells was 47.42% when treated with Sorafenib (10 μmol/L) monotherapy, and 46.04% when treated with cisplatinum (10 mg/L) monotherapy. When Sorafenib(10 μmol/L) was combined with cisplatinum (10 mg/L), the cellular proliferation and survival rate was only 16.71% ( P <0.05). qPCR and western blot revealed that a combination of Sorafenib (10 μmol/L) and cisplatinum (10 mg/L) reduced the transcription and protein expression of autophagy-related AKT and mTOR but increased that of LC3 (P <0.05). Conclusion: Combining Sorafenib and cisplatinum can effectively induce cell autophagy and reduce cellular proliferation via the PI3K/AKT/mTOR signal pathway.
Highlights
We found that the survival rate of HepG2 cells was 47.42% when treated with Sorafenib (10 μmol/L) monotherapy, and 46.04% when treated with cisplatinum (10 mg/L) monotherapy
When Sorafenib(10 μmol/L) was combined with cisplatinum (10 mg/L), the cellular proliferation and survival rate was only 16.71% ( P
A combination of Sorafenib and cisplatinum inhibited the transcription of key enzymes in the PI3K/AKT/mTOR signaling and autophagy regulation pathways
Summary
HCC is preferentially treated using a surgery based, comprehensive treatment plan (Lau et al, 2014). These treatments have their drawbacks (Chen and Zhu, 2016; Lau et al, 2014; Gedaly et al, 2013 ).Cell autophagy is a conservative mechanism used to maintain homeostasis which can be impaired by aging, with excessive cellular autophagy often resulting in uncontrolled cell death. The PI3K/AKT/mTOR signaling pathway is a critical component in HCC mediated autophagy, making it an ideal therapeutic target. Sorafenib can inhibit cell proliferation via alterations in PI3K/AKT/mTOR signaling (He et al, 2015). The aim of this study was to evaluate the effect of a combined Sorafenib/cisplatinum therapeutic on HCC proliferation and autophagy, and to determine their effect on PI3K/AKT/mTOR signaling
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