Abstract. Overexpression of ABCG2 is considered a major mechanism of cancer drug resistance. Recent studies have shown that ABCG2 can regulate the switch between symmetric and asymmetric cell division in adult stem cells; however, the relationship between ABCG2 and cell division in drugresistant cancer cells remains to be determined. In the present study, we demonstrated that ABCG2 is involved in the cell division of drug-resistant cancer cells. We first established drug-resistant H460 and A549 cell lines by repeated exposure to cisplatin and found that the expression of ABCG2 in these cell lines was significantly increased. As evidenced by PKH-26 staining, these drug-resistant cell lines favored symmetric division, which differed from the asymmetric division of the parental cells. Furthermore, we established stable ABCG2-overexpressing and stable shRNA-ABCG2-knockdown cell lines to evaluate the potential role of ABCG2 in cancer cell division. The results showed that overexpression of ABCG2 in A549 parental cells significantly increased the proportion of symmetric division, whereas knockdown of ABCG2 in drug-resistant A549 cells significantly increased the proportion of asymmetric division. Taken together, our findings suggest that ABCG2 is involved in the modulation of cancer drug resistance by regulating the pattern of cell division. The present study provides novel insight into the role of ABCG2 in cancer treatment resistance. IntroductionChemotherapy is a key method of treatment in the primary and palliative care of patients with lung cancer, of which non-small cell lung cancer (NSCLC) accounts for the majority of cases. Cisplatin is one of the most common chemotherapeutic drugs for lung cancer treatment, particularly for NSCLC; however, many patients have resistance to cisplatin initially and secondarily (1,2). To overcome drug resistance, patients with NSCLC are administered large doses of drugs, which induce numerous adverse effects and fail to improve the clinical prognosis. Therefore, a better understanding of the molecular mechanisms underlying cisplatin resistance is warranted to further clarify the exact mechanisms underlying chemoresistance and to find or design efficient drugs to improve individual chemotherapy strategies for NSCLC patients.Increasing studies have shown that the active effluence of chemotherapeutic drugs from cancer cells is one of the main mechanisms of drug resistance. Cancer cells often exhibit drug resistance with the overexpression of membrane transport proteins, which effectively pump antitumor drugs out (3). The ATP-binding cassette (ABC) multi-drug transporters, such as ABCG2 (BCRP/MXR/ABCP), are considered to be responsible for the bulk of drug efflux in human cancer (4). Moreover, the overexpression of ABCG2 has been reported to confer drug resistance upon NSCLC to various chemotherapeutic drugs (5). Furthermore, a previous study also showed ABCG2 to be closely associated with clinical outcome in platinum-based chemotherapy for advanced NSCLC patients. For example, ABCG2-...

Background/Aims: Nicotinamide plays a protective role in hypoxia-induced cardiomyocyte dysfunction. However, the underlying molecular mechanisms remain poorly understood. The purpose of this study was to investigate these and the effect of nicotinamide pretreatment on hypoxic cardiomyocytes. Methods: Cultured rat cardiomyocytes were pretreated with nicotinamide, subjected to hypoxia for 6 h, and then cell necrosis and apoptosis were examined. The effects of nicotinamide pretreatment on hypoxia-induced reactive oxygen species (ROS) formation, antioxidant enzyme expression, nicotinamide adenine dinucleotide (NAD⁺) and nicotinamide adenine dinucleotide phosphate (NADP⁺) levels, adenosine triphosphate (ATP) production and mitochondrial membrane potential were tested to elucidate the underlying mechanisms. Results: Based on the findings that nicotinamide treatment decreased protein expression of receptor-interacting protein (RIP; a marker for cell necrosis) and cleaved caspase-3 (CC3; a marker for cell apoptosis) in normoxic cardiomyocytes, we found that it dramatically reduced hypoxia-induced necrosis and apoptosis in cardiomyocytes. The underlying mechanisms of these effects are associated with the fact that it increased protein expression of superoxide dismutase and catalase, increased intracellular levels of NAD⁺ and ATP concentration, decreased mitochondrial ROS generation and prevented the loss of mitochondrial membrane potential. Conclusion: All of these results indicate that nicotinamide pretreatment protects cardiomyocytes by improving mitochondrial stress. Our study provides a new clue for the utilization of nicotinamide in therapies for ischemic heart disease.