Artesunate exerts an anti-immunosuppressive effect on cervical cancer by inhibiting PGE2 production and Foxp3 expression.
Artesunate (ART), derived from a common traditional Chinese medicine, has beeen used an antimalarial for several years. In this study, the effect and mechanism of ART on anti-human cervical cancer cells was examined. The level of prostaglandin E2 (PGE2 ) and the population of CD4+CD25+Foxp3 regulatory T cells (Treg) in peripheral blood were detected by flow cytometry. In vivo antitumor activity was investigated in mice with cervical cancer by the subcutaneous injection of various concentrations of ART. The concentrations of PGE2 in the supernatants of CaSki cells were measured using an ELISA kit. Cyclooxygenase-2 (COX-2) and Foxp3 expression were determined using quantitative polymerase chain reaction (qPCR) and western blot analysis. The effect of ART on the viability of CaSki and Hela cells was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. It was identified that the level of PGE2 and the population of CD4+CD25+Foxp3 Treg cells in the peripheral blood were significantly higher in cervical cancer patients and mice with cervical cancer. ART was capable of inhibiting orthotopic tumor growth, which correlated with a decrease in the level of PGE2 and the percentage of Treg cells in mice with cervical cancer. Furthermore, ART decreased COX-2 expression and the production of PGE2 in CaSki and Hela cells. Notably, the supernatants of CaSki cells treated with ART lowered the expression of Foxp3 in Jurkat T cells, which was capable of being reversed by exogenous PGE2 . Our data revealed that ART may elicit an anti-tumor effect against cervical cancer by inhibition of PGE2 production in CaSki and Hela cells, which resulted in the decrease of Foxp3 expression in T cells. Therefore, ART may be an effective drug for immunotherapy of cervical cancer.
Department of Reproductive Medicine, Taizhou People's Hospital Affiliated of Nantong University of Medicine, Taizhou, 225300, China; Department of Gynecology, Taizhou People's Hospital Affiliated of Nantong University of Medicine, Taizhou, 225300, China.
Li-Xin
LX
Zhang
Zhi-Neng
ZN
Liu
Jun
J
Ye
Min
M
Sha
Hua
H
Qian
Xin-Hua
XH
Bu
Zheng-Yun
ZY
Luan
Xin-Lan
XL
Xu
Ai-Hua
AH
Huang
Dong-Lan
DL
Yuan
Yi-Qun
YQ
Wu
Xiao-Xiang
XX
Wang
Jia
J
Wang
Jun-Xing
JX
Huang
Li-Hua
LH
Ye
D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005260:Female; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects* / Q000502:physiology; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D002583:Uterine Cervical Neoplasms / Q000378:metabolism
D037621:Artemisinins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D000077332:Artesunate; D015232:Dinoprostone
Foxp3; PGE2; artesunate; cervical cancer; immunotherapy