Gambogenic Acid Exerts Antitumor Activity in Hypoxic Multiple Myeloma Cells by Regulation of miR-21

Liu, Ping; Wu, Xue; Dai, Lu; Ge, Zheng; Gao, Chong; Zhang, Hongming; Wang, Fei; Zhang, Xiaoping; Chen, Baoan

doi:10.7150/jca.19290

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J Cancer 2017; 8(16):3278-3286. doi:10.7150/jca.19290 This issue Cite

Research Paper

Gambogenic Acid Exerts Antitumor Activity in Hypoxic Multiple Myeloma Cells by Regulation of miR-21

Ping Liu, Xue Wu, Lu Dai, Zheng Ge, Chong Gao, Hongming Zhang, Fei Wang, Xiaoping Zhang^✉, Baoan Chen^✉

Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, People's Republic of China.

✉ Corresponding authors: Xiaoping Zhang, Department of Hematology and Oncology (Key Department of Jiangsu Medicine), Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, People's Republic of China Tel +86 25 83262473 E-mail violet More

Citation:

Liu P, Wu X, Dai L, Ge Z, Gao C, Zhang H, Wang F, Zhang X, Chen B. Gambogenic Acid Exerts Antitumor Activity in Hypoxic Multiple Myeloma Cells by Regulation of miR-21. J Cancer 2017; 8(16):3278-3286. doi:10.7150/jca.19290. https://www.jcancer.org/v08p3278.htm

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Abstract

Hypoxia is an inseparable component of the bone marrow (BM) microenvironment, accounting for aggressive tumor behavior and poor prognosis of multiple myeloma (MM). Gambogenic acid (GNA) has proven to be an attractive option for treatment of tumors due to its tumor suppressive activity. Herein, we found that GNA exhibits remarkable apoptotic activity against MM cells even under hypoxia. MicroRNA-21 (miR-21) has been found over-expressed in MM patients and associated with the occurrence and development of MM. Direct studies have shown that there is a functional link between hypoxia and miR-21 expression in multiple types of tumors. In the current study, we found that hypoxia increased miR-21 expression in U266 cells and miR-21 induced by hypoxia was associated with concurrent reductions in its target PTEN. After treatment with GNA, miR-21 expression in hypoxic U266 cells was strikingly downregulated in a dose-dependent manner. Besides, we identified that regulation of miR-21/PTEN by GNA under hypoxia is related with inhibition of HIF-1α accumulation and STAT3 phosphorylation. Furthermore, in vivo study revealed that intravenous GNA injection could significantly suppress tumor growth and the miR-21/PTEN pathway is involved in GNA's anti-tumor effects. Taken together, all these results indicated that GNA could be a highly potent therapeutic for human MM.

Keywords: Multiple myeloma, bone marrow, Gambogenic acid

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APA

Liu, P., Wu, X., Dai, L., Ge, Z., Gao, C., Zhang, H., Wang, F., Zhang, X., Chen, B. (2017). Gambogenic Acid Exerts Antitumor Activity in Hypoxic Multiple Myeloma Cells by Regulation of miR-21. Journal of Cancer, 8(16), 3278-3286. https://doi.org/10.7150/jca.19290.

ACS

Liu, P.; Wu, X.; Dai, L.; Ge, Z.; Gao, C.; Zhang, H.; Wang, F.; Zhang, X.; Chen, B. Gambogenic Acid Exerts Antitumor Activity in Hypoxic Multiple Myeloma Cells by Regulation of miR-21. J. Cancer 2017, 8 (16), 3278-3286. DOI: 10.7150/jca.19290.

NLM

CSE

Liu P, Wu X, Dai L, Ge Z, Gao C, Zhang H, Wang F, Zhang X, Chen B. 2017. Gambogenic Acid Exerts Antitumor Activity in Hypoxic Multiple Myeloma Cells by Regulation of miR-21. J Cancer. 8(16):3278-3286.

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