Antitumor Activity of Asiaticoside Against Multiple Myeloma Drug-Resistant Cancer Cells Is Mediated by Autophagy Induction, Activation of Effector Caspases, and Inhibition of Cell Migration, Invasion, and STAT-3 Signaling Pathway

积雪草苷对多发性骨髓瘤耐药癌细胞的抗肿瘤活性是通过诱导自噬、激活效应胱天蛋白酶以及抑制细胞迁移、侵袭和 STAT-3 信号通路介导的

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作者:Li Yingchun, Wang Huihan, Zhang Rong, Zhang Guojun, Yang Ying, Liu Zhuogang

Abstract

BACKGROUND Accumulating evidence suggests that plant-derived molecules may prove extremely beneficial in the development of chemotherapy for deadly cancer types. Multiple myeloma is a rare and incurable type of cancers. Very little research has been directed towards the development of chemotherapy for the management of multiple myeloma. Here, the anticancer effects of a plant-derived triterpenoid, Asiaticoside, were examined against the drug-resistant myeloma cell line KM3/BTZ. MATERIAL AND METHODS Cell viability was determined by CCK-8 assay and autophagy was checked by transmission electron microscopy. ROS levels were determined by flow cytometery. Cell migration and invasion were examined by Transwell assay. Protein expression was assessed by Western blotting. RESULTS The results showed that Asiaticoside inhibits the growth of the KM3/BTZ cells and exhibited an IC₅&sub0; of 12 µM. Further, it was observed that the anticancer effects of Asiaticoside are due to the induction of autophagy allied with upsurge of the expression of LC3-II. Moreover, the expression of the effector caspases in the KM3/BTZ cells was also altered. Asiaticoside also caused accretion of the ROS in the KM3/BTZ cells and inhibited their migratory and invasive properties via modulation of the STAT-3 signaling pathway. CONCLUSIONS Asiaticoside may prove useful in the management and treatment of the multiple myeloma and needs further investigation.

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