J Cancer 2019; 10(16):3778-3788. doi:10.7150/jca.30359 This issue Cite

Research Paper

Anti-tumor Drug THZ1 Suppresses TGFβ2-mediated EMT in Lens Epithelial Cells via Notch and TGFβ/Smad Signaling Pathway

Jie Ning1, Xinqi Ma1, Chongde Long1, Yuxiang Mao1, Xielan Kuang1,2, Zixin Huang1, Yuting Fan1, Han Zhang1, Qing Xia1, Renchun Wang3, Yu Liang4, Shuibin Lin4, Qingjiong Zhang1, Huangxuan Shen1,2✉

1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie Road, Guangzhou 510060, China.
2. Biobank of Eye, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie Road, Guangzhou 510060, China.
3. The Second Clinical Medicine School of Lanzhou University, No.199, West Donggang Road, Lanzhou, Gansu Province, 730000, China.
4. Center for Translational Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

Citation:
Ning J, Ma X, Long C, Mao Y, Kuang X, Huang Z, Fan Y, Zhang H, Xia Q, Wang R, Liang Y, Lin S, Zhang Q, Shen H. Anti-tumor Drug THZ1 Suppresses TGFβ2-mediated EMT in Lens Epithelial Cells via Notch and TGFβ/Smad Signaling Pathway. J Cancer 2019; 10(16):3778-3788. doi:10.7150/jca.30359. https://www.jcancer.org/v10p3778.htm
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Abstract

Selective covalent CDK7 inhibitor THZ1 is a promising potential anti-tumor drug in many kinds of cancers. Epithelial-mesenchymal Transition (EMT) is highly related to cancer initiation, development, invasion and metastasis and other pathogenesis processes. We treated cancer cell line Hela229 and three retinoblastoma cell lines so-RB50, WERI-Rb-1, Y79 with gradient concentration of THZ1, and found that THZ1 could inhibit cell viability and EMT, suggesting that THZ1 may be a promising drug for human cervical cancer and retinoblastoma treatment. Our results verified the role of THZ1 in EMT for the first time, however, the mechanism needs further study. Here we report that THZ1 suppresses the TGFβ2 induced EMT in human SRA01/04 lens epithelial cells (LECs), rabbit primary lens epithelial cells, and whole rat lens culture semi-in vivo model. RNA-sequencing and KEGG analysis revealed that the THZ1 inhibits EMT by down-regulating phosphorylate Smad2 and Notch signaling pathway. On the other hand, we found that THZ1 could strongly inhibit LECs proliferation through G2/M phase arrest as well as attenuating of MAPK, PI3K/AKT signaling pathway. Our results uncovered the function and underlying mechanism of THZ1 in regulation of EMT, which provides a new perspective of the anti-tumor effect by THZ1 and may offer a novel treatment for PCO.

Keywords: anti-tumor, THZ1, epithelial-mesenchymal transition, Notch, TGFβ/Smad signaling pathway


Citation styles

APA
Ning, J., Ma, X., Long, C., Mao, Y., Kuang, X., Huang, Z., Fan, Y., Zhang, H., Xia, Q., Wang, R., Liang, Y., Lin, S., Zhang, Q., Shen, H. (2019). Anti-tumor Drug THZ1 Suppresses TGFβ2-mediated EMT in Lens Epithelial Cells via Notch and TGFβ/Smad Signaling Pathway. Journal of Cancer, 10(16), 3778-3788. https://doi.org/10.7150/jca.30359.

ACS
Ning, J.; Ma, X.; Long, C.; Mao, Y.; Kuang, X.; Huang, Z.; Fan, Y.; Zhang, H.; Xia, Q.; Wang, R.; Liang, Y.; Lin, S.; Zhang, Q.; Shen, H. Anti-tumor Drug THZ1 Suppresses TGFβ2-mediated EMT in Lens Epithelial Cells via Notch and TGFβ/Smad Signaling Pathway. J. Cancer 2019, 10 (16), 3778-3788. DOI: 10.7150/jca.30359.

NLM
Ning J, Ma X, Long C, Mao Y, Kuang X, Huang Z, Fan Y, Zhang H, Xia Q, Wang R, Liang Y, Lin S, Zhang Q, Shen H. Anti-tumor Drug THZ1 Suppresses TGFβ2-mediated EMT in Lens Epithelial Cells via Notch and TGFβ/Smad Signaling Pathway. J Cancer 2019; 10(16):3778-3788. doi:10.7150/jca.30359. https://www.jcancer.org/v10p3778.htm

CSE
Ning J, Ma X, Long C, Mao Y, Kuang X, Huang Z, Fan Y, Zhang H, Xia Q, Wang R, Liang Y, Lin S, Zhang Q, Shen H. 2019. Anti-tumor Drug THZ1 Suppresses TGFβ2-mediated EMT in Lens Epithelial Cells via Notch and TGFβ/Smad Signaling Pathway. J Cancer. 10(16):3778-3788.

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