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 células humanas de cáncer colorrectal mediante la regulación de la vía de señalización SIRT3/PI3K/AKT.

• Xiaodong Shen Minhang Hospital Affiliated to Fudan University, Xinzhuang Town, Shanghai, China. https://orcid.org/0009-0000-0520-8896
• Chencheng Shi Minhang Hospital Affiliated to Fudan University, Xinzhuang Town, Shanghai, China. https://orcid.org/0009-0008-1369-2946
• Ming Lei Minhang Hospital Affiliated to Fudan University, Shanghai, China. https://orcid.org/0009-0000-8480-197X
• Rongjian Zhou Minhang Hospital Affiliated to Fudan University, Xinzhuang Town, Shanghai, China. https://orcid.org/0009-0007-5598-0834
• Shaoqun Liu Minhang Hospital Affiliated to Fudan University, Xinzhuang Town, Shanghai, China. https://orcid.org/0000-0002-2016-0947
• Chang Su Minhang Hospital Affiliated to Fudan University, Xinzhuang Town, Shanghai, China. https://orcid.org/0009-0004-6481-2638

DOI: https://doi.org/10.54817/IC.v65n3a01

Keywords: dihydroartemisinin, SIRT3, oxaliplatin, colorectal cancer

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 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.

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