Dihydroartemisinin, an artemisinin derivative, reverses oxaliplatin resistance in human colorectal cancer cells by regulating the SIRT3/PI3K/AKT signalling pathway.

Abstract

Abstract. Dihydroartemisinin (DHA), a derivative of artemisinin, has been shown to act as a chemosensitizer of various cancer chemotherapeutic agents both in vitro and in vivo. However, in colorectal cancer (CRC), no study has fo-cused on the effect of DHA on oxaliplatin (L -OHP) resistance. Our study aimed to examine the effectiveness of DHA in reversing the resistance of human CRC cells to L -OHP, as well as its underlying molecular mechanisms. LoVo cells were purchased from ATCC, while LoVo/L -OHP cells were obtained by exposing LoVo cells to progressively increasing concentrations of L -OHP. LoVo/L -OHP were treated with various concentrations of DHA, and cell apoptosis ratio and vi-ability were assessed by flow cytometry and CCK-8. Our results showed that DHA treatment remarkably decreased the viability of LoVo/L -OHP cells and increased the apoptosis ratio. As the mechanism of action, we found that DHA enhanced the expression of Sirtuin 3 (SIRT3) and suppressed the phosphati-dylinositol 3-kinase (PI3K)/AKT signalling cascade. Silencing of SIRT3 reversed the effect of DHA on cell apoptosis and viability by activating the PI3K/AKT axis in LoVo/L -OHP cells. Overall, our study found that DHA has the ability to counteract L -OHP resistance in LoVo/L -OHP cells through the modulation of the SIRT3/PI3K/AKT signalling pathway, suggesting a new research target for CRC treatment.