Zihao Zhu

Radiation therapy is an important method to treat liver cancer, but because of the strong DNA repair ability of liver cancer cells, even after receiving high doses of radiation still can not get satisfactory results. Atorvastatin (ATO) is a lipophilic and tissue-selective inhibitor of HMG-CoA reductase whose anticancer effects have been validated in various cells, but its effect on the radiation sensitivity of hepatocellular carcinoma cells remains unclear. Therefore, Therefore, this study explored the radiosensitivity of ATO and its possible mechanism by pretreating HepG2 with ATO and collecting HepG2 cells after irradiation. It was found that atorvastatin can not only affect the survival of liver cancer cells when used alone, but also enhance the radiation sensitivity of HepG2 cells. The study found that ATO significantly exacerbated the inhibitory effects of IR on the growth, proliferation, and migration of HepG2 cells. Measurement of ROS, SOD, GPx, and MDA levels indicated that ATO enhanced IR-induced oxidative stress, further promoted the decrease of Mitochondrial Membrane Potential, increased the rate of apoptosis in HepG2, upregulating pro-apoptotic proteins Bax and Cleaved-Caspase 3, and downregulating anti-apoptotic proteins Bcl-2. Western blot analysis showed that the PI3K-Akt–mTOR pathway was inhibited, leading to the activation of cytotoxic autophagy in HepG2 and an increase in the expression of the LC-3II protein. In summary, ATO, in combination with IR, enhances the oxidative stress response of HepG2 induced by IR, promotes autophagy by inhibiting the PI3K-Akt–mTOR pathway, and thereby potentially enhances the radiosensitivity of HepG2 as a pharmacological intervention.

Background: The protective effects of astragaloside IV (ASIV) on various diseases are well known, but its potential impact on radiation-induced bystander effect (RIBE) has remained unclear. Objective: This study aimed to explore the protective mechanism of ASIV against oxidative damage caused by RIBE in LO2 cells. Methods: To construct the RIBE model, the conditioned medium from HepG2 cells irradiated with radiation was transferred to nonirradiated LO2 cells. LY294002, a commonly used phosphatidylinositol 3-kinase/Akt pathway inhibitor, was added to LO2 cells 1 h before exposing HepG2 cells to radiation. LO2 cells were then collected for analyses after RIBE exposure. Results: The study found that ASIV significantly improved cell proliferation and promoted the recovery of mitochondrial membrane potential while reducing the rate of apoptosis. Western blot analyses demonstrated that ASIV upregulated B-cell lymphoma 2 and downregulated B-cell lymphoma 2-related X protein and cleaved-caspase 3. Measurement of reactive oxygen species, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels showed that ASIV effectively restored the oxidative stress state induced by RIBE. Additionally, immunofluorescence and western blots analyses confirmed that ASIV enhanced the translocation of Nrf2 to the nucleus and activated downstream nicotinamide adenine dinucleotide phosphate: quinine oxidoreductase 1 and heme oxygenase 1. Importantly, Akt pathway inhibitor repressed ASIV-induced activation of Nrf2 and its protective effect against RIBE. Conclusion: This study demonstrates that ASIV protects LO2 cells against oxidative damage caused by RIBE through activation of the Akt/Nrf2 pathway.