J Cancer 2018; 9(1):117-128. doi:10.7150/jca.21965 This issue Cite

Research Paper

Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma

Weiwen Liu1*, Xian-lu Song2*, Shan-chao Zhao3, Minyi He4, Hai Wang5 6, Ziyang Chen5,6, Wei Xiang5,6, Guozhong Yi5,6, Songtao Qi5,6✉, Yawei Liu5,6✉

1. First College of Clinical Medicine, Southern Medical University, Guangzhou 510515, China;
2. Department of Radiotherapy, Guangzhou Medical University Cancer Institute and Hospital, Guangzhou 510095, China;
3. Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;
4. Center for Clinical Medical Education, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;
5. Department of Neurosurgery, Nanfang hospital, Southern Medical University, Guangzhou 510515, China;
6. Laboratory for Precision Neurosurgery, Nanfang hospital, Southern Medical University, Guangzhou 510515, China.
* Weiwen Liu and Xianlu Song contribute equally.

Citation:
Liu W, Song Xl, Zhao Sc, He M, Wang H, Chen Z, Xiang W, Yi G, Qi S, Liu Y. Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma. J Cancer 2018; 9(1):117-128. doi:10.7150/jca.21965. https://www.jcancer.org/v09p0117.htm
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Abstract

Ethnopharmacological relevance: Dapivirine is one of reverse transcriptase inhibitors (RTIs). It is the prototype of diarylpyrimidines (DAPY), formerly known as TMC120 or DAPY R147681 (IUPAC name: 4- [[4-(2, 4, 6-trimethylphenyl) amino]-2-pyrimidinyl] amino]-benzonitrile; CAS no.244767-67-7).

Aim: The purpose of this study is to investigate the antitumor activity of dapivirine, one of the RTIs, on U87 glioblastoma (GBM) cells in vitro and in vivo.

Materials and Methods: U87 GBM cells were cultured and treated with or without dapivirine. Cell viability was evaluated by CCK-8 (Cell Counting Kit 8, CCK-8) assay; apoptosis was analyzed by flow cytometry; cell migration was evaluated by Boyden Chamber assay; Western blotting was performed to detect proteins related to apoptosis, epithelial-to-mesenchymal transition and autophagy. PathScan intracellular signaling array kit was used to detect important and well-characterized signaling molecules. Tumor xenograft model in nude mice was used to evaluate the antitumorigenic effect in vivo.

Results: Dapivirine weakened proliferation of glioma cells and induced the apoptosis of U87 glioblastoma cells. Furthermore, dapivirine regulated autophagy and induced Akt, Bad and SAPK/JNK activations. Moreover, the inhibition of glioma cell growth by dapivirine was also observed in nude mice in vivo.

Conclusion: In summary, in our study dapivirine exposure induces stress, resulting in JNK and PI3K/Akt pathway activation through diminished inhibition of the apoptosis and autophagy cascade in U87 GBM cells, which inhibits cell growth in vitro and in vivo.

Keywords: Dapivirine, Antitumor activity, Drug metabolism, Glioblastoma, Autophagy


Citation styles

APA
Liu, W., Song, X.l., Zhao, S.c., He, M., Wang, H., Chen, Z., Xiang, W., Yi, G., Qi, S., Liu, Y. (2018). Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma. Journal of Cancer, 9(1), 117-128. https://doi.org/10.7150/jca.21965.

ACS
Liu, W.; Song, X.l.; Zhao, S.c.; He, M.; Wang, H.; Chen, Z.; Xiang, W.; Yi, G.; Qi, S.; Liu, Y. Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma. J. Cancer 2018, 9 (1), 117-128. DOI: 10.7150/jca.21965.

NLM
Liu W, Song Xl, Zhao Sc, He M, Wang H, Chen Z, Xiang W, Yi G, Qi S, Liu Y. Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma. J Cancer 2018; 9(1):117-128. doi:10.7150/jca.21965. https://www.jcancer.org/v09p0117.htm

CSE
Liu W, Song Xl, Zhao Sc, He M, Wang H, Chen Z, Xiang W, Yi G, Qi S, Liu Y. 2018. Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma. J Cancer. 9(1):117-128.

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