缺氧通过刺激胸腺基质淋巴细胞生成素分泌促进宫颈癌细胞体外侵袭

摘要

Objective:To explore the effects of hypoxia and thymic stromal lymphopoietin (TSLP) on the invasion of cervical cancer cells in vitro.Methods:Enzyme linked immunosorbent assay (ELISA) was performed to analyze the effects of normoxia and hypoxia on the secretion level of TSLP, and to analyze the effects of recombinant human TSLP (rhTSLP) protein on the expression levels of matrix metalloprotein-2 (MMP-2), MMP-9, and IL-8 in cervical cancer cell lines HeLa and CaSki.Matrigel invasion assay was used to investigate the effects of rhTSLP, hypoxia, and anti-human TSLP (aTSLP) neutralizing antibody (aTSLP, 5 μg/mL) on the invasiveness of HeLa and CaSki cells in vitro.Results:Under hypoxia exposure, the levels of TSLP secretion in HeLa and CaSki cells were significantly increased (P<0.01).RhTSLP (100 ng/mL) stimulation in vitro significantly enhanced the invasiveness of HeLa and CaSki cells (P<0.001), and promoted the productions of MMP-2, MMP-9, and IL-8 (P<0.01).The invasiveness of HeLa and CaSki cells can be promoted significantly under hypoxia exposure (P<0.001).In contrast, aTSLP (5 μg/mL) inhibited the invasiveness of HeLa and CaSki cells (P<0.05), and partly inhibited the stimulatory effect of hypoxia on invasiveness of HeLa and CaSki cells (P<0.05).Conclusions:Hypoxia facilitates the invasion of cervical cancer cells in vitro by up-regulating the secretion of TSLP.%目的:探讨缺氧诱导宫颈癌细胞体外侵袭的可能调节机制.方法:用ELISA法分析常氧和缺氧培养对宫颈癌细胞株HeLa和CaSki细胞的胸腺基质淋巴细胞生成素(thymic stromal lymphopoietin, TSLP)分泌水平及TSLP对侵袭相关分子基质金属蛋白酶-2(matrix metalloprotein-2, MMP-2)、MMP-9和白细胞介素-8(interleukin-8, IL-8)表达水平的影响.Matrigel侵袭实验分别检测重组TSLP、缺氧和TSLP中和性抗体对宫颈癌细胞侵袭力的影响.结果:与常氧环境相比,缺氧培养下HeLa、CaSki细胞TSLP分泌水平显著升高,差异有统计学意义(P<0.01).重组TSLP(100 ng/mL)体外刺激显著促进HeLa、CaSki细胞的侵袭力(P<0.001),并促进其分泌MMP-2、MMP-9和IL-8(P<0.01).缺氧培养可显著促进HeLa、CaSki细胞的侵袭力(P<0.001);TSLP中和性抗体(5 μg/mL)能抑制HeLa、CaSki细胞侵袭(P<0.05),且可明显抑制缺氧对HeLa、CaSki细胞侵袭力的促进作用(P<0.05).结论:缺氧可通过促进宫颈癌细胞分泌TSLP,促进宫颈癌细胞体外侵袭.