Emodin Ameliorates the Efficacy of Carfilzomib in Multiple Myeloma Cells via Apoptosis and Autophagy

大黄素通过细胞凋亡和自噬增强卡非佐米对多发性骨髓瘤细胞的疗效

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作者:Chin-Mu Hsu, Chia-Hung Yen, Shu-Chen Wang, Yi-Chang Liu, Chien-Tzu Huang, Min-Hong Wang, Tzer-Ming Chuang, Ya-Lun Ke, Tsung-Jang Yeh, Yuh-Ching Gau, Jeng-Shiun Du, Hui-Ching Wang, Shih-Feng Cho, Yuhsin Tsai, Chi-En Hsiao, Samuel Yien Hsiao, Hui-Hua Hsiao

Background

Carfilzomib, the proteasome inhibitor, can increase the overall survival rate of multiple myeloma (MM) patients undergoing targeted therapy. However, relapse and toxicity present great challenges for such treatment, so an urgent need for effective combination therapy is necessary. Emodin is a natural chemical compound that inhibits the proliferation of various cancers and can effectively combine with other treatments. In this study, we evaluated the sensitizing effect of emodin combined with carfilzomib on MM cells.

Conclusions

These results provide a molecular target for combination therapy in MM patients.

Methods

The cells were treated with emodin, carfilzomib, and a combination of drugs to determine their effects on cell proliferation and viability. The cell cycle distribution and reactive oxygen species (ROS) expression were measured by flow cytometry. The level of RNA and protein were analyzed through real-time qPCR and immunoblotting.

Results

Emodin acted synergistically with carfilzomib to reduce the proliferation and viability of MM cell lines in vitro. Furthermore, the combination of emodin and carfilzomib increased ROS production, inducing apoptosis and autophagy pathways via caspase-3, PARP, p62, and LC3B. Conclusions: These results provide a molecular target for combination therapy in MM patients.

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