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.
Background The Ubiquitin-Proteasome system (UPS) pathway plays a crucial role in the degradation of protein. PSMD13 is a crucial subunit of proteasome S11 regulatory granules and plays an indispensable role in the UPS. However, its role in tumors was still sealed. Our research mainly to study its expression level and effect on the prognosis of LIHC, what pathways PSMD13 works through and how it relates to the level of immune cells. Methods Our exploration mainly used GEPIA, Kaplan-Meier Plotter to discover the differentially expressed level of PSMD13 in multiple cancers and surrounding tissue. In the further study of LIHC, we also downloaded the data from the TCGA database. We used R software for multivariate analysis to explore the value of PSMD13 in the prognosis of LIHC. In studying its pathway, we used GSEA to analyze. We also used TISIDB, TIMER to observe its relationship and immune molecules in LIHC. Results PSMD13 is differentially expressed in many cancers including LIHC. In LIHC, PSMD13 was an independent prognostic factor. The PSMD13 is likely to take effect upon the regulation of oxidative phosphorylation and proteasome pathway. Besides, the high-level expression of PSMD13 is also relevant to the infiltration of CD8 + T cells and macrophages. Conclusions In LIHC, PSMD13 may play an important role in regulating cell cycle and recruitment of immune cells. In addition, PSMD13 may be a reliable biomarker to judge the response to immunotherapy and prognosis of patients with LIHC.
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