Dihydroartemisinin, an artemisinin derivative, reverses oxaliplatin resistance in human colorectal cancer cells by regulating the SIRT3/PI3K/AKT signalling pathway/La dihidroartemisinina, un derivado de la artemisinina, revierte la resistencia al oxaliplatino en celulas humanas de cancer colorrectal mediante la regulacion de la via de senalizacion SIRT3/PI3K/AKT

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 focused 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 viability 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 phosphatidylinositol 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. Keywords: dihydroartemisinin; SIRT3; oxaliplatin; colorectal cancer. Se ha demostrado que la dihidroartemisinina (DHA), un derivado de la artemisinina, actua como quimiosensibilizador de diversos agentes quimioterapeuticos contra el cancer tanto in vitro como in vivo. Sin embargo, en el cancer colorrectal (CCR), ningun estudio se ha centrado en el efecto del DHA sobre la resistencia al oxaliplatino (L-OHP). El objetivo de nuestro estudio era examinar la eficacia del DHA para revertir la resistencia de las celulas humanas de CCR al L-OHP, asi como sus mecanismos moleculares subyacentes. Las celulas LoVo se adquirieron a ATCC, mientras que las celulas LoVo/L-OHP se obtuvieron exponiendo las celulas LoVo a concentraciones progresivamente crecientes de L-OHP. Las celulas LoVo/L-OHP se trataron con diversas concentraciones de DHA, y el indice de apoptosis celular y la viabilidad se evaluaron mediante citometria de flujo y CCK-8. Nuestros resultados mostraron que el tratamiento con DHA disminuia notablemente la viabilidad de las celulas LoVo/L-OHP y aumentaba el indice de apoptosis. Desde el punto de vista de s