PRL-3 antibody combined with pemetrexed induces apoptosis of human lung adenocarcinoma cell line A549

Abstract

Abstract: Objective To investigate the effects of PRL-3 antibody and pemetrexed on proliferation, migration and apoptosis of A549 cells. Methods A549 cells were treated with PRL-3 antibody at different concentrations; CCK-8 method was used to measure the cell proliferation of human lung adenocarcinoma A549 cells in each group; Transwell chamber assay was used to detect cell migration ability of A549 cells; Flow cytometry assay was used to measure the apoptosis rate of A549 cells; PRL-3, P-ERK and VEGF protein expressions of A549 cells were detected by Western bolt. Results 1)Compared with the control group, the inhibitory effect of PRL-3 antibody on proliferation of A549 cells increased with the increase of PRL-3 concentration (P＜0.05); 2)The inhibitory effect of the combination group on proliferation and migration ability of A549 cells was more significant than that of the monotheraphy group (P＜0.05); 3)The apoptosis rate of A549 cells in the combination group 34.63%±1.65% was better than that of PRL-3 antibody group 17.24%±1.15% and pemetrexed group 15.32%±1.82% (P＜0.05); 4)Compared with the monotheraphy group, the expressions of PRL-3, P-ERK and VEGF proteins in the combination group decreased more significantly (P＜0.05). Conclusions PRL-3 antibody combined with pemetrexed can inhibit the proliferation, migration and induce apoptosis of A549 cells as compared to the monotherapy group. The mechanism may be attributed to the inhibition of the expressions of PRL-3, P-ERK and VEGF protein.

Key words: lung cancer, pemetrexed, PRL-3, P-ERK, VEGF

CLC Number:

R734.2

SHENG Xin, LIU Dan, DENG Shu-kai. PRL-3 antibody combined with pemetrexed induces apoptosis of human lung adenocarcinoma cell line A549[J]. Basic & Clinical Medicine, 2020, 40(5): 678-683.

References

[1]Abdelaziz HM, Elzoghby AO, Helmy MW, et al. Liquid crystalline assembly for potential combinatorial chemo-herbal drug delivery to lung cancer cells[J]. Int J Nanomedicine, 2019,14:499-517.
[2]Tanaka T, Kaida T, Yokoi K, et al. Critical relevance of genomic gains of PRL-3/EGFR/c-myc pathway genes in liver metastasis of colorectal cancer[J]. Oncol Lett, 2019,17:1257-1266.
[3]Chong PSY, Zhou J, Chooi JY, et al. Non-canonical activation of beta-catenin by PRL-3 phosphatase in acute myeloid leukemia[J]. Oncogene, 2019,38:1508-1519.
[4]张丹,王立民,王红阳,等.人肺腺癌A549细胞系培美曲塞耐药细胞株模型的建立[J].临床肺科杂志, 2016,21:893-895.
[5]Tanino R, Tsubata Y, Harashima N, et al. Novel drug-resistance mechanisms of pemetrexed-treated non-small cell lung cancer[J]. Oncotarget, 2018,9:16807-16821.
[6]Miura K, Oba T, Hamanaka K, et al. FGF2-FGFR1 pathway activation together with thymidylate synthase upregulation is induced in pemetrexed-resistant lung cancer cells[J]. Oncotarget,2019,10:1171-1192.
[7]Chiu LY, Hsin IL, Yang TY, et al. The ERK-ZEB1 pathway mediates epithelial-mesenchymal transition in pemetrexed resistant lung cancer cells with suppression by vinca alkaloids [J]. Oncogene, 2017,36:242-253.
[8]Zhang Y, Li Z, Fan X, et al. PRL-3 promotes gastric cancer peritoneal metastasis via the PI3K/AKT signaling pathway in vitro and in vivo[J]. Oncol Lett, 2018,15:9069-9074.
[9]Zhang C, Qu L, Lian S, et al. PRL-3 promotes ubiquitination and degradation of AURKA and colorectal cancer progression via dephosphorylation of FZR1[J].Cancer Res, 2019,79:928-940.
[10]Radke I, Götte M, Smollich M, et al. Expression of PRL-3 regulates proliferation and invasion of breast cancer cells in vitro[J]. Arch Gynecol Obstet, 2017,296:1153-1160.
[11]Hjort MA, Hov H, Abdollahi P, et al. Phosphatase of regenerating liver-3 (PRL-3) is overexpressed in classical Hodgkin lymphoma and promotes survival and migration[J]. Exp Hematol Oncol, 2018,7: 1153-1160.
[12]Hjort MA, Abdollahi P, Vandsemb EN, et al. Phospha-tase of regenerating liver-3 is expressed in acute lymphoblastic leukemia and mediates leukemic cell adhesion, migration and drug resistance[J]. Oncotarget, 2017,9:3549-3561.
[13]Ye L, Pu C, Tang J, et al. Transmembrane-4 L-six family member-1 (TM4SF1) promotes non-small cell lung cancer proliferation, invasion and chemo-resistance through regulating the DDR1/Akt/ERK-mTOR axis[J]. Respir Res, 2019,20:1071-1075.
[14]Hwang JJ, Min SH, Sin KH, et al. Altered expression of phosphatase of regenerating liver gene family in non-small cell lung cancer [J]. Oncol Rep, 2012 ,27:535-540.
[15]Mu N, Gu J, Liu N, et al. PRL-3 is a potential glioblastoma prognostic marker and promotes glioblastoma progression by enhancing MMP7 through the ERK and JNK pathways[J]. Theranostics, 2018,8:1527-1539.