目的:探讨同源框A10（HOXA10）基因在子宫内膜癌组织中的表达及其对子宫内膜癌Ishikawa 细胞株凋亡、迁移及侵袭的影响。方法：收集2012 年至2013 年在鼓楼医院妇产科子宫内膜癌组织标本21 例、正常增殖期子宫内膜组织标本25 例，采用实时荧光定量PCR(qRT-PCR)及Western blotting 方法检测HOXA10 在子宫内膜癌组织及正常子宫内膜组织中的表达。将感染复数为5、10、20 MOI的ad-flag-HOXA10 腺病毒质粒及20 MOI的ad-flag-lacz 腺病毒质粒(对照组)感染人子宫内膜癌Ishikawa 细胞株，流式细胞术检测各组细胞凋亡情况。将50 nmol/L的si-HOXA10 及si-NC质粒转染Ishikawa 细胞株，分别为下调组及下调对照组；将20 MOI的ad-flag-HOXA10 及20 MOI的ad-flag-lacz 腺病毒质粒感染Ishikawa 细胞株，分别为上调组及上调对照组；Transwell 小室检测各组细胞迁移及侵袭能力。结果：在子宫内膜癌组织中HOXA10 mRNA 表达量比正常子宫内膜组织中显著降低[ （0.56±0.14）vs (1.36±0.33)，P<0.01]，其蛋白表达量同样显著降低[ （1.01±0.25）vs (2.10±0.71)，P<0.01]。上调HOXA10后5、10、20 MOI 组细胞的凋亡率明显升高，且大多数处于早期凋亡[ （50.92±8.79）%、(55.17±4.07)%、(76.10±3.65)% vs (7.74±0.15)%，均P<0.01]。下调HOXA10 表达后迁移细胞数显著增加[ （248±25）vs (135±15)个，P<0.01]，上调HOXA10 表达后迁移细胞数显著减少[（50±6）vs (100±13) 个，P<0.01]；下调HOXA10 表达后侵袭细胞数显著增多[ （131±18）vs (66±9)个，P<0.01]，上调HOXA10 表达后侵袭细胞数显著减少[ （34±8）vs（60±4）个，P<0.01]。结论：HOXA10 基因在子宫内膜癌内膜中表达低于正常内膜，子宫内膜癌Ishikawa细胞株中上调HOXA10 基因表达能促进细胞凋亡并抑制其迁移和侵袭能力。

Objective: To study the expression of HOXA10 gene in endometrial carcinoma and its effect on the apoptosis, migration and invasion of Ishikawa cells. Methods: Twenty-one cases of endometrial carcinoma tissue samples and 25 cases of normal endometrial tissue samples from patients treated at the Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital from 2012 to 2013 were collected for this study. The mRNA and protein expressions of HOXA10 in endometrial carcinoma and normal endometrial tissues were separately tested by Realtime-qPCR (qRT-PCR) and Western blotting. Ishikawa cells were infected with adenovirus-flag-HOXA10 at different multiplicity (5, 10, 20 MOI), and infected by adenovirus-flag-lacz (20 MOI) as control; And the cell apoptosis was tested by Flow Cytometry. Ishikawa cells were transfected with 50 nmol/L si-HOXA10 plasmids and 50 nmol/L si-NC plasmids, as down-regulation group and down-regulation control group, respectively. Ishikawa cells were infected with 20 MOI adenovirus-flag-HOXA10 and 20 MOI adenovirus-flag-lacz, as up-regulation group and up-regulation control group, respectively. The ability of migration and invasion was detected by transwell assay. Results: The results of qRT-PCR and Western blotting showed that the expressions of HOXA10 mRNA and protein in endometrial carcinoma samples were both significantly lower than normal samples [mRNA: (0.56±0.14)vs (1.36±0.33), P<0.01; protein: (1.01±0.25) vs (2.10±0.71), P<0.001]. After the up-regulation of HOXA10 gene in Ishikawa cell line, the cell apoptosis rate in ad-flag-HOXA10 groups (5, 10, 20 MOI) was significantly raised, and most of which was in the early apoptosis [(50.92±8.79)%, (55.17±4.07)%, (76.10±3.65)% vs (7.74 ± 0.15)%, all P<0.01]. The number of migrated cells was markedly up-regulated in si-HOXA10 group [(248±25) vs (135±15), P<0.01] but markedly down-regulated in ad-flag-HOXA10 group [(50±6) vs (100±13), P<0.01]. The number of invasive cells was markedly up-regulated in si-HOXA10 group [(131±18) vs (66±9), P<0.01] but markedly down-regulated in ad-flag-HOXA10 group [(34±8) vs (60±4), P<0.01]. Conclusions: Both mRNA and protein expressions of HOXA10 were down-regulated in endometrial carcinoma samples than in normal endometrium. Up-regulation of HOXA10 gene in Ishikawa cell line can promote cell apoptosis and inhibit cell migration and invasion.

江苏省自然科学基金资助项目（No. BK20151096）