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| Effect of six-segment transmembrane epithelial antigen of prostate 4 on proliferation of prostate cancer cells in inflammatory environment |
| SUN Xinghua1 YU Tao2 ZHANG Xuexin3 CHANG Hongyan1 HONG Yueguang1 LI Weiwei4 |
1.Department of Oncology, Qinhuangdao Hospital of Traditional Chinese Medicine, Hebei Province, Qinhuangdao 066000, China;
2.College of Life Sciences and Technology, Weifang Medical University, Shandong Province, Weifang 261053, China;
3.Department of Cardiovascular Medicine, Qinhuangdao Hospital of Traditional Chinese Medicine, Hebei Province, Qinhuangdao 066000, China;
4.Department of Reproductive Medicine, Qinhuangdao Maternal and Child Health Care Hospital, Hebei Province, Qinhuangdao 066000, China |
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Abstract Objective To investigate the role of six-segment transmembrane epithelial antigen of prostate 4 (STEAP4) in the development of prostate cancer in the inflammatory microenvironment induced by lipopolysaccharide (LPS). Methods The inflammatory environment of prostate cancer cells PC3 and VCaP was induced by LPS. PC3 and VCaP cells were divided into control group, LPS treated group (PC3 and VCaP cells were exposed to 1 μg/ml LPS), transfection control group(LPS+transfection si-con) and transfection silence group (LPS+transfection si-STEAP4). The STEAP4 level was detected 24 h after transfection by Western blot. The expression levels of cytokines interleukin (IL)-6, IL-8 and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay. Cell proliferation was detected by CCK-8 and EdU staining. The expression level of cyclic guanosine monophosphate(cGMP)-cGMP-dependent protein kinase(PKG) signaling pathway related proteins was detected by Western blot. Results STEAP4 protein expression level of PC3 and VCaP cells in LPS treated group was significantly higher than that in control group (P＜0.05). There was no significant difference in the expression level of STEAP4 protein in PC3 and VCaP cells in LPS treated group compared with transfection control group (P＞0.05). The expression level of STEAP4 protein in PC3 and VCaP cells in transfection silence group was significantly lower than that in transfection control group (P＜0.05). The expression levels of IL-6, IL-8, and TNF-α in PC3 and VCaP cells in LPS treated group were significantly higher than those in control group (P＜0.05). There were no significant differences in the expression levels of IL-6, IL-8, and TNF-α in PC3 and VCaP cells between LPS treated group and transfection control group (P＞0.05). The expression levels of IL-6, IL-8, and TNF-α in PC3 and VCaP cells in transfection silence group were significantly lower than those in transfection control group (P＜0.05). The proliferation activity of PC3 and VCaP cells in LPS treated group was significantly higher than that in control group at 24, 48, and 72 h (P＜0.05). There was no significant difference in the proliferation activity of PC3 and VCaP cells at 24, 48, and 72 h between LPS treated group and transfection control group (P＞0.05). The proliferation activity of PC3 and VCaP cells in transfection silence group was lower than that in transfection control group at 24, 48, and 72 h (P＜0.05). The proliferation activity of PC3 and VCaP cells in LPS treated group was significantly higher than that in control group (P＜0.05). There was no significant difference in the proliferation activity of PC3 and VCaP cells between LPS treated group and transfection control group (P＞0.05). The proliferation activity of PC3 and VCaP cells in transfection silence group was significantly lower than that in transfection control group (P＜0.05). The relative expression levels of cGMP, PKG1, PKG2, and phosphorylated vasodilator stimulated phosphoprotein (pVASP)/VASP in PC3 and VCaP cells of LPS treated group were significantly lower than those of control group (P＜0.05). There were no significant differences in the relative expression levels of cGMP, PKG1, PKG2, and pVASP/VASP in PC3 and VCaP cells between transfection control group and LPS treated group (P＞0.05). The relative expression levels of cGMP, PKG1, PKG2, and pVASP/VASP in PC3 and VCaP cells of transfection silence group were significantly higher than those of transfection control group (P＜0.05). Conclusion STEAP4 silencing inhibits the proliferation and inflammatory response of prostate cancer cells induced by LPS. Downregulation of STEAP4 may inhibit LPS-induced tumorigenesis by reducing cell proliferation and inflammatory response.
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[1] Sung H，Ferlay J，Siegel RL，et al. Global Cancer Statistics 2020：GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries [J]. CA Cancer J Clin，2021，71（3）：209-249.
[2] Song XD，Wang YN，Zhang AL，et al. Advances in research on the interaction between in?覲ammation and cancer [J]. J Int Med Res，2020，48（4）：300060519895347.
[3] Cai T，Santi R，Tamanini I，et al. Current knowledge of the potential links between in?覲ammation and prostate cancer [J]. Int J Mol Sci，2019，20（15）：3833.
[4] Lin YS，Tsai KL，Chen JN，et al. Mangiferin inhibits lipopoly- saccharideinduced epithelial-mesenchymal transition（EMT）and enhances the expression of tumor suppressor gene PER1 in non-small cell lung cancer cells [J]. Environ Toxicol，2020， 35（10）：1070-1081.
[5] Chen Z ，Liu Q ，Zhu Z，et al. Ursolic acid protects against proliferation and in?覲ammatory response in LPS-treated gastric tumour model and cells by inhibiting NLRP3 in?覲ammasome activation [J]. Cancer Manag Res，2020，12（9）：8413-8424.
[6] Jiang XY，Yuan J，Dou，YY ，et al. Lipopolysaccharide affects the proliferation and glucose metabolism of cervical cancer cells through the FRA1/MDM2/p53 pathway [J]. Int J Med Sci，2021，18（4）：1030-1038.
[7] Liu CM，An L，Wu Z，et al. 6-Gingerol suppresses cell viab- ility，migration and invasion via inhibiting EMT，and inducing autophagy and ferroptosis in LPS-stimulated and LPS- unstimulated prostate cancer cells [J]. Oncol Lett，2022，23（6）：187.
[8] Xing WY，Zhang ZH，Xu S，et al. Calcitriol inhibits lipopo- lysaccharide-induced proliferation，migration and invasion of prostate cancer cells through suppressing STAT3 signal activation [J]. Int Immunopharmacol，2020，82（2）：106346.
[9] Zhao Z，Wang Z，Song Z，et al. Share Predictive potential of STEAP family for survival，immune microenvironment and therapy response in glioma [J]. Int Immunopharmacol，2021， 101（Pt A）：108183.
[10] Wu HT，Chen WJ，Xu Y，et al. The tumor suppressive roles and prognostic values of STEAP family members in breast cancer [J]. Biomed Res Int，2020，82（3）：9578484.
[11] Yan D，Dong W，He QQ ，et al. Circular RNA circPICALM sponges miR-1265 to inhibit bladder cancer metastasis and in?覲uence FAK phosphorylation [J]. EBioMedicine，2019，48（10）：316-331.
[12] Fang ZX，Li CL，Chen WJ，et al. Potential of six-transmembrane epithelial antigen of the prostate 4 as a prognostic marker for colorectal cancer [J]. World J Gastrointest Oncol，2022，14（9）：1675-1688.
[13] Burnell SEA，Spencer-Harty S，Howarth S，et al. Utilisation of the STEAP protein family in a diagnostic setting may pro- vide a more comprehensive prognosis of prostate cancer [J]. PLoS One，2019，14（8）：e0220456.
[14] Xu PY，Cai F，Liu XF，et al. Sesamin inhibits lipopolysac- charide-induced proliferation and invasion through the p38-MAPK and NF-κB signaling pathways in prostate cancer cells [J]. Oncol Rep，2019，33（6）：3117-3123.
[15] Echeverri M，Felder K，Anderson D，et al. Fostering shared decision-making about prostate cancer screening among African American men patients and their primary care providers：a randomized behavioral clinical trial [J]. Trials，2022，23（1）：653.
[16] Tian QX，Zhang ZH.，Ye QL，et al. Melatonin inhibits migration and invasion in LPS-stimulated and -unstimulated prostate cancer cells through blocking multiple EMT-relative pathways [J]. J In?覲amm Res，2021，14（2）：2253-2265.
[17] Tolani MA，Suleiman A，Awaisu M，et al. Acute urinary tract infection in patients with underlying benign prostatic hyperplasia and prostate cancer [J]. Pan Afr Med J，2020， 36（10）：169.
[18] Banerjee S，Alwine JC，Wei Z，et al. Microbiome signatures in prostate cancer [J]. Carcinogenesis，2019，40（8）：749-764.
[19] Ou T，Lilly M，Jiang W. The pathologic role of toll-like rece- ptor 4 in prostate cancer [J]. Front Immunol，2018，9（10）：4-10.
[20] Lee CF，Dang A，Hernandez E，et al. Activation of sphingosine kinase by lipopolysaccharide promotes prostate cancer cell invasion and metastasis via SphK1/S1PR4/matriptase [J]. Oncogene，2019，38（28）：5580-5598.
[21] Liao Y，Zhao J，Bulek K，et al. inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL- 17-STEAP4-XIAP axis [J]. Nat Commun，2020，11（1）：900.
[22] Ebe H，Matsumoto I，Osada A，et al. Splice variant of STE- AP4 localizes in the nucleus，making it a possible transcriptional regulator of IL-6 production [J]. Mod Rheumatol，2019，29（4）：714-716.
[23] Sikkeland J，Ng MYW，Nenseth HZ，et al. STAMP2 suppresses autophagy in prostate cancer cells by modulating the integrated stress response pathway [J]. Am J Cancer Res， 2022，12（1）：327-336.
[24] Pihlstrom N，Jin Y，Nenseth Z，et al. STAMP2 expression mediated by cytokines attenuates their growth-limiting effects in prostate cancer cells [J]. Cancers（Basel），2021，13（7）：1579.
[25] 林小淇，邱晓拂，袁雪峰，等.炎症小体NLRP3调控LPS诱导的前列腺癌增殖和侵袭的机制研究[J].解剖学研究，2023，44（6）：544-550.
[26] Xu H，Zhang Z，Li P ，et al. Expression of PKG2 in ovarian cancer and its effect on epidermal growth factor receptor [J]. J BUON，2020，25（12）：729-735. |
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