Homoharringtonine inhibited breast cancer cells growth via miR-18a-3p/AKT/mTOR signaling pathway

Li-bin Wang^1*, Dan-ni Wang^1,2*, Li-gang Wu¹, Jia Cao¹, Jin-hai Tian¹, Rong Liu¹, Rong Ma¹, Jing-jing Yu¹, Jia Wang¹, Qi Huang¹, Wen-yong Xiong^1,3✉, Xu Zhang^1✉

1. The General Hospital of Ningxia Medical University, Biochip Research Center, Yinchuan, 750001, China.
2. Gansu Provincial Hospital, Clinical Laboratory Center, Lanzhou, 730000, China.
3. Key Laboratory of Medicinal Chemistry for Natural Resource, Yunnan University, Kunming, 650091, China.
*These authors contributed equally to this work.

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Citation:
Wang Lb, Wang Dn, Wu Lg, Cao J, Tian Jh, Liu R, Ma R, Yu Jj, Wang J, Huang Q, Xiong Wy, Zhang X. Homoharringtonine inhibited breast cancer cells growth via miR-18a-3p/AKT/mTOR signaling pathway. Int J Biol Sci 2021; 17(4):995-1009. doi:10.7150/ijbs.44907. Available from https://www.ijbs.com/v17p0995.htm

Abstract

Homoharringtonine (HHT), a natural alkaloid derived from the cephalotaxus, exhibited its anti-cancer effects in hematological malignancies clinically. However, its pesticide effects and mechanisms in treating solid tumors remain unclear. In this study, we found that HHT was capable of inhibiting tumor growth after 5-days treatment of breast cancer cells, MCF-7, in vivo. Furthemore, HHT also significantly inhibited the cancer cell growth and induced cell apoptosis in vitro. miRNA sequencing proved miR-18a-3p was noticeably downregulated in the cells after HHT treatment. Moreover, downregulating miR-18a-3p increased HHT-induced cell apoptosis; our data supported that HHT suppressed miR-18a-3p expression and inhibited tumorigenesis might via AKT-mTOR signaling pathway. In conclusion: our study proved that HHT suppressed breast cancer cell growth and promoted apoptosis mediated by regulating of the miR-18a-3p-AKT-mTOR signaling pathway, HHT may be a promising antitumor agent in breast cancer treatment.

Keywords: HHT, breast cancer, miR-18a-3p, AKT-mTOR signal pathway