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J Cancer. 2018 Jan 1;9(1):117-128. doi: 10.7150/jca.21965. eCollection 2018.

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

Liu W1, Song XL2, Zhao SC3, He M4, Wang H5,6, Chen Z5,6, Xiang W5,6, Yi G5,6, Qi S5,6, Liu Y5,6.

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First College of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
Department of Radiotherapy, Guangzhou Medical University Cancer Institute and Hospital, Guangzhou 510095, China.
Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Center for Clinical Medical Education, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Department of Neurosurgery, Nanfang hospital, Southern Medical University, Guangzhou 510515, China.
Laboratory for Precision Neurosurgery, Nanfang hospital, Southern Medical University, Guangzhou 510515, China.



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).


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.


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.


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.


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.


Antitumor activity; Autophagy; Dapivirine; Drug metabolism; Glioblastoma

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

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