Effect of papaverine on radiosensitivity of hepatocellular carcinoma cells by regulating autophagy

Abstract

Background Liver cancer is a common malignant tumor. Radiotherapy is a promising treatment for patients with liver cancer. Autophagy, as a tumor defense mechanism, can often affect the therapeutic effect of tumor, while papaverine has been found to inhibit the growth of liver cancer cells.Methods In order to explore the mechanism of papaverine and autophagy in radiosensitivity of primary hepatocellular carcinoma, HepG2 and Huh7 cells were irradiated by X-ray and divided into negative control group (NC), papaverine group (PPV) and simple irradiation group (IR). Cell proliferation was detected by CCK8 test, cell migration was detected by scratch test, radiosensitivity was detected by clone formation test, and LC3 Ⅱ and ATG7 were detected by RT-PCR test. MRNA expression and autophagy related markers LC3, p62, p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR protein expression were detected by Western-blotting.Results Compared with NC group, papaverine significantly inhibited the proliferation of hepatoma HepG2 and Huh7 cells. Papaverine could inhibit the migration ability of hepatoma cells. Papaverine could significantly decrease the expression of LC3 Ⅱ and ATG7mRNA, decrease the protein expression of LC3 Ⅱ / LC3I, and increase the protein expression of p62, p-PI3K, p-AKT and p-mTOR. Papaverine can also improve the effect of radiotherapy on liver cancer cells.Conclusions Papaverine inhibits autophagy of HepG2 and Huh7 cells through PI3K/AKT/mTOR pathway, so as to inhibit the proliferation and migration of hepatocellular carcinoma cells and improve the radiosensitivity of hepatocellular carcinoma cells.