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

Palabras clave: dihidroartemisinina, SIRT3, oxaliplatino, cáncer colorrectal

Resumen

Se ha demostrado que la dihidroartemisinina (DHA), un derivado de la artemisinina, actúa como quimiosensibilizador de diversos agentes quimioterapéuticos contra el cáncer tanto in vitro como in vivo. Sin embargo, en el cáncer colorrectal (CCR), ningún 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 células humanas de CCR al L -OHP, así como sus mecanismos moleculares subyacentes. Las células LoVo se adquirieron a ATCC, mientras que las células LoVo/L -OHP se obtuvieron exponiendo las células LoVo a concentraciones progresivamente crecientes de L -OHP. Las células LoVo/L -OHP se trataron con diversas con-centraciones de DHA, y el índice de apoptosis celular y la viabilidad se evalua-ron mediante citometría de flujo y CCK-8. Nuestros resultados mostraron que el tratamiento con DHA disminuía notablemente la viabilidad de las células LoVo/L -OHP y aumentaba el índice de apoptosis. Desde el punto de vista de su mecanismo de acción, se observó que el DHA potenciaba la expresión de la sirtuina 3 (SIRT3) y suprimía la cascada de señalización fosfatidilinositol 3-ci-nasa (PI3K)/AKT. El silenciamiento de SIRT3 revirtió el efecto del DHA sobre la apoptosis y la viabilidad celular a través de la activación del eje PI3K/AKT en las células LoVo/L -OHP. En conjunto, nuestro estudio descubrió la capacidad del DHA para contrarrestar la resistencia a L -OHP en células LoVo/L -OHP a través de la modulación de la vía de señalización SIRT3/PI3K/AKT, lo cual sugiere una nueva foco de investigación para el tratamiento del CCR.

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