Mechanisms of Progesterone on Proliferation and Migration of Human Ovarian Cancer Cells via HOXA9

Xiaoyan YANG; Chunguang HAO; Zhijian ZHANG

doi:10.12259/j.issn.2095-610X.S20221022

Volume 43 Issue 10

Oct. 2022

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Xiaoyan YANG, Chunguang HAO, Zhijian ZHANG. Mechanisms of Progesterone on Proliferation and Migration of Human Ovarian Cancer Cells via HOXA9[J]. Journal of Kunming Medical University, 2022, 43(10): 35-42. doi: 10.12259/j.issn.2095-610X.S20221022

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Xiaoyan YANG, Chunguang HAO, Zhijian ZHANG. Mechanisms of Progesterone on Proliferation and Migration of Human Ovarian Cancer Cells via HOXA9[J]. Journal of Kunming Medical University, 2022, 43(10): 35-42. doi: 10.12259/j.issn.2095-610X.S20221022

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Mechanisms of Progesterone on Proliferation and Migration of Human Ovarian Cancer Cells via HOXA9

doi: 10.12259/j.issn.2095-610X.S20221022

1.
Dept. of Pathology，Inner Mongolia Baogang Group Third Staff Hospital，Baotou Inner Mongolia
2.
Dept. of Anesthesiology，Inner Mongolia Baogang Hospital，Baotou Inner Mongolia
3.
Dept. of Pathology，Inner Mongolia Baogang Hospital， Baotou Inner Mongolia 014016, China

Received Date: 2022-06-17
Available Online: 2022-10-09
Publish Date: 2022-10-31

Abstract

Abstract

Objective To investigate the mechanism of HOXA9 in the process of progesterone inhibition of ovarian cancer progression. Methods （1） Human ovarian cancer cell line HO-8910 were cultured according to the gradient of progestin medroxyprogesterone acetate （MPA） concentration （0.1, 1, 10, 50 and 100 μmol/L）, and the cell morphology was observed after 24 h, 48 h and 72 h. CCK-8 was used to detect cell viability and determine IC50. The apoptosis rate was detected by Annexin V-FITC double staining. （2） H0-8910 were divided into four groups: 1） NC group; 2） progestin group; 3） progestin+si-HOXA9 group; 4） progestin+ov-HOXA9 group. H0-8910 cells were transfected with HOXA9 knockdown or overexpression plasmids and treated with MPA or not transfected with plasmids alone using MPA for 72 h. The qPCR and western blot were used to detect the mRNA and protein expression of HOXA9. as well as the expression of epithelial mesenchymal transition （EMT）-related proteins （Vimentin, N-cadherin, E-cadherin）, respectively. Wound scratch assay was used to detect cell migration; Transwell assay was used to detect cell invasion. Results （1） After progesterone stimulation, the growth status of HO-8910 became poor, the arrangement was sparse, cell proliferation, migration and invasion ability were suppressed （P < 0.0001）, and the apoptosis rate increased （P < 0.0001）; （2） calculated by cck8 results, the IC50 value of H0-8910 cells treated with MPA for 72 h was 2.680 μmol/L; （3） compared with human ovarian epithelial cells CP- H055, HOXA9 mRNA was highly expressed in human ovarian cancer cell lines HO-8910, SKOV3, A2780 and OVCAR3 （P < 0.01）, and HOXA9 protein was likewise highly expressed in HO-8910 （P < 0.001）; （4） progesterone could inhibit HOXA9 expression （P < 0.0001）, and the inhibition of cell invasion and migration ability by progesterone was more obvious after knocking down HOXA9 （P < 0.0001）, while the inhibition of HO-8910 invasion and migration ability was slightly reduced after overexpression of HOXA9 （P < 0.0001）. （5） Progesterone increased E-cadherin protein expression （P < 0.01）, while Vimentin and N-cadherin protein expression decreased （P < 0.001）; after knocking down HOXA9, the effect of progesterone on EMT-related protein expression in HO-891 was more obvious （P < 0.05）, while after overexpressing HOXA9, the effect of progesterone on EMT-related protein expression in HO-891 was weakened （P < 0.05）. Conclusion Progesterone inhibits the development of ovarian cancer by suppressing the expression of HOXA9 gene and therefore suppressing the malignant biological phenotypes such as cell proliferation, migration, invasion and EMT process.
- Ovarian cancer,
- HOXA9,
- Progesterone,
- Medroxyprogesterone acetate

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References(30)

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