Chemotherapy resistance in ovarian cancer is related to multiple mechanisms, including DNA repair, autophagy, metabolic reprogramming, multidrug resistance gene expression, epithelial-mesenchymal transition, etc. In recent years, a large number of studies have found that reduced glutathione (GSH) is also involved in the drug resistance process of ovarian cancer chemotherapy. GSH has multiple roles in cells, acting as a reactive oxygen species (ROS) scavenger, xenobiotic antidote, and cysteine reservoir. The biological role of GSH has two sides. On the one hand, it can maintain normal cell homeostasis; on the other hand, it can reduce the damage of chemotherapy drugs to tumor cells and promote chemotherapy resistance.
The GSH antioxidant system promotes chemoresistance in ovarian cancer by inhibiting chemotherapeutic drug-induced oxidative stress. Compared with normal cells, tumor cells produce more ROS during metabolism and are in a state of oxidative stress for a long time. Chemotherapy drugs cause tumors to produce further oxidative stimulation on the basis of oxidative stress, causing irreversible changes in cellular lipids, proteins and DNA. damage, leading to tumor cell death. Long-term chemotherapeutic drug treatment often enhances the antioxidant system in tumor cells, leading to chemotherapeutic drug resistance.
GSH and its related metabolic enzymes constitute the most important antioxidant defense system in the body, protecting cells from ROS attacks. This feature provides conditions for tumor cells to become resistant to chemotherapy. Recent studies have shown that chemotherapy resistance is closely related to the increase of GSH and its related metabolic enzymes. Asare-Werehene et al found that drug-resistant cell lines produced higher levels of intracellular GSH compared with sensitive ovarian cancer cell lines. The high concentration and high reactivity of GSH in tumor cells lead to chemotherapy resistance through anti-oxidative stress. In melanoma cells, inhibition of GSH can significantly promote oxidative stress, increase cytotoxicity, and promote cell death. The above studies have shown that GSH can promote ovarian cancer chemotherapy resistance by inhibiting chemotherapy drug oxidative stress.