| 张永丽,王晴,张晶波,等.胎球蛋白 A通过 MAPK信号通路抑制卵巢癌迁移行为及机制研究[J].安徽医药,2024,28(12):2438-2442. |
| 胎球蛋白 A通过 MAPK信号通路抑制卵巢癌迁移行为及机制研究 |
| AHSG inhibits the migration of ovarian cancer through MAPK/ERK signaling pathway |
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| DOI：10.3969/j.issn.1009-6469.2024.12.021 |
| 中文关键词: 卵巢肿瘤 胎球蛋白类 生物信息学分析 迁移 MAPK信号通路 |
| 英文关键词: Ovarian neoplasms Fetuins Bioinformatic analysis Migration MAPK signal pathway |
| 基金项目:江苏省新药研究与临床药学重点实验室课题( XZSYSKF2022007) |
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| 中文摘要: |
| 目的探讨胎球蛋白 A(AHSG)对卵巢癌细胞迁移行为的影响及分子机制。方法收取 2022年 9月至 2023年 1月于徐州市中心医院冻存的正常卵巢组织标本及卵巢癌组织标本。通过 UALCAN数据库检索 AHSG在卵巢癌中的表达情况；通过蛋白质印迹法检测临床卵巢癌组织及正常卵巢组织标本中 AHSG蛋白表达水平，免疫组织化学染色检测卵巢癌及正常卵巢组织石蜡切片中 AHSG蛋白表达水平；以卵巢癌细胞系 SKOV3细胞、 HO8910细胞作为研究对象，通过病毒转染技术构建上调 AHSG表达的 SKOV3细胞、 HO8910细胞，通过伤口愈合实验、 Transwell实验检测对照组及 AHSG过表达组细胞迁移能力；蛋白质印迹法检测 AHSG过表达后对促分裂原活化的蛋白质激酶( MAPK)通路关键蛋白 c-Jun氨基端激酶( JNK)、磷酸化( p-)JNK、 p38丝裂原激活的蛋白激酶( p38 MAPK)、 p-p38 MAPK、胞外信号调节激酶( ERK)、 p-ERK的影响。结果 UALCAN数据库显示 AHSG在卵巢癌中低表达；蛋白质印迹法结果显示卵巢癌组织中 AHSG蛋白表达水平显著降低( P<0.05)。免疫组织化学染色实验显示 AHSG蛋白表达水平在卵巢癌组织中显著下降( 2.11±0.63比 12.41±1.04，P<0.05)。伤口愈合实验显示过表达 AHSG可显著抑制卵巢癌 SKOV3细胞［( 14.92±5.72)%比( 45.07±7.07)%］、 HO8910细胞［( 56.31±2.37)%比( 64.30±1.76)%］的迁移能力( P<0.05)； Transwell实验显示过表达 AHSG可显著抑制卵巢癌 SKOV3细胞［( 110.00±4.36)个比( 201.33±23.18)个］、 HO8910细胞［( 119.00±16.64)个比( 167.00±6.08)个］的迁移能力( P<0.05)。上调 AHSG可显著抑制 MAPK信号通路关键蛋白的表达，在 SKOV3细胞中， p-p38 MAPK/p38 MAPK(1.03±0.22比 1.67±0.15)、 p-JNK/JNK(0.75±0.27比 1.25±0.15)、 p-ERK/ERK(0.55±0.11比 1.01±0.22)(P<0.05)。同样在 HO8910细胞中， p-p38 MAPK/p38 MAPK(0.42±0.02比 1.11 ± 0.28)、 p-JNK/JNK(0.73±0.12比 0.99±0.11)、 p-ERK/ERK(0.94±0.20比 1.69±0.13)(P<0.05)。结论 AHSG可以抑制卵巢癌细胞迁移能力，其作用机制可能与 AHSG抑制 MAPK通路的激活有关。 |
| 英文摘要: |
| Objective To investigate the effect of Alpha-2 Heremans Schmid Glycoprotein (AHSG) on the migration of ovarian cancer cells and its molecular mechanism.Methods The collection of normal ovarian tissue specimens and ovarian cancer tissue specimenswere cryopreserved at Xuzhou Central Hospital from September 2022 to January 2023. The expression of AHSG in ovarian cancer wasretrieved from the UALCAN database; The expression levels of AHSG in clinical ovarian cancer tissues and normal ovarian tissueswere detected by Western blot experiment. And the expression of AHSG protein in paraffin sections of ovarian cancer and normal ovari-an tissues were detected by the immunohistochemical method. SKOV3 cells and HO8910 cells were selected as the research subjects.SKOV3 cells and HO8910 cells with up-regulated AHSG expression were constructed by virus transfection technique. The migrationability of control group and AHSG overexpression group was detected by wound healing assay and Transwell assay. Western blottinganalysis was used to detect the effects of overexpression of AHSG on the MAPK pathway key proteins, Jun N-terminal kinase (JNK), phosphorylated Jun N-terminal kinase (p-JNK), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylated p38 mitogen-activat-ed protein kinase (p-p38 MAPK), extracellular signal-regulated kinase (ERK), and phosphorylated extracellular signal-regulated kinase (p-ERK).Results UALCAN database showed the low expression of AHSG in ovarian cancer. Compared with normal ovarian tissues, Western blot showed that the expression level of AHSG protein was significantly decreased in ovarian cancer tissues (P<0.05). Immuno-histochemical method showed that the expression of AHSG protein in the ovarian cancer group was lower than the normal group (2.11±0.63 vs. 12.41±1.04, P<0.05). The wound healing experiment showed that overexpression of AHSG could significantly inhibit the migra-tion ability of SKOV3 [(14.92±5.72)% vs. (45.07±7.07)%] and HO8910 cells [(56.31±2.37)% vs. (64.30±1.76)%] (P<0.05). Transwellassay also showed that overexpression of AHSG could significantly inhibit the migration ability of SKOV3 (110.00±4.36 vs. 201.33± 23.18) and HO8910 cells (119.00±16.64 vs. 167.00±6.08) (P<0.05). Up-regulation of AHSG could significantly inhibit the key proteins of MAPK signaling pathway. The relative expression of p-p38 MAPK/p38 MAPK (1.03±0.22 vs. 1.67±0.15), p-JNK/JNK (0.75±0.27 vs. 1.25±0.15), p-ERK/ERK (0.55±0.11 vs. 1.01±0.22) in the SKOV3 cells (P<0.05). Similarly, the relative expression of p-p38 MAPK/ p38 MAPK (0.42±0.02 vs. 1.11±0.28), p-JNK/JNK (0.73±0.12 vs. 0.99±0.11), p-ERK/ERK (0.94±0.20 vs. 1.69±0.13) were also found in the HO8910 cells (P<0.05). Conclusion AHSG can inhibit ovarian cancer cell migration, and its mechanism may be related toAHSG can inhibit the activation of MAPK pathway. |
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