硫酸右旋糖苷对子宫内膜癌细胞生物学行为的影响
The Effect of Dextran Sulfate on the Biological Behavior of Endometrial Cancer Cells
DOI: 10.12677/ACM.2022.122118, PDF,    科研立项经费支持
作者: 冯楠竹：大连医科大学妇产科，辽宁 大连；张裕民：菏泽市食品药品检验检测研究院，山东 菏泽；李 稳：青岛大学，山东 青岛 ；郭 丽, 张 萍*：青岛市市立医院妇科，山东 青岛
关键词: 硫酸右旋糖苷；子宫内膜癌细胞；增殖；迁移；凋亡；Dextran Sulfate； Endometrial Cancer Cells； Proliferation； Migration； Apoptosis
摘要: 目的：探讨硫酸右旋糖苷(DS)对子宫内膜腺癌细胞(HEC-1A、Ishikawa)增殖、迁移、侵袭及凋亡的影响及可能的相关分子机制。方法：培养子宫内膜腺癌细胞(HEC-1A、Ishikawa)，设立对照组与实验组，分别予以培养基与相应浓度DS处理，采用平板克隆形成实验、CCK8实验检测DS对细胞增殖能力的影响；划痕实验检测DS对细胞迁移能力的影响；Transwell侵袭实验检测DS对细胞侵袭能力的影响；流式细胞术检测DS对细胞凋亡率的影响；Western Blot实验验证DS对细胞凋亡蛋白(Bax、Bcl-2)表达的影响。结果：CCK8实验结果显示，与对照组相比，实验组(0.2%、0.4%、0.6%、0.8% DS)肿瘤细胞增殖明显减少(P < 0.05)；克隆形成实验结果显示，与对照组相比，实验组(0.8% DS)肿瘤细胞集落形成数量明显减少(P < 0.05)；划痕实验结果显示，与对照组相比，实验组(0.8% DS)划痕愈合率均明显降低(P < 0.05)；Transwell侵袭实验结果显示，与对照组相比，实验组(0.8% DS)细胞侵袭能力明显降低(P < 0.05)；流式细胞术结果显示，与对照组相比，实验组(0.8% DS)细胞凋亡率明显增加(P < 0.05)。Western Blot实验结果显示，与对照组相比，实验组(0.8% DS)凋亡蛋白Bax表达水平增加，抗凋亡蛋白Bcl-2表达水平明显降低(P < 0.05)，Bax/Bcl-2比值明显升高(P < 0.05)。结论：DS能够抑制子宫内膜腺癌细胞(HEC-1A、Ishikawa)的增殖、迁移、侵袭能力，促进细胞凋亡。
Abstract: Objective: To investigate the effects of dextran sulfate (DS) on the proliferation, migration, invasion and apoptosis of endometrial cancer cells (HEC-1A, Ishikawa) and the possible related molecular mechanisms. Methods: Human endometrial cancer cells (HEC-1A, Ishikawa) were cultured, the control groups were treated with culture medium, and the experimental groups were treated with DS in corresponding concentration, respectively. The effect of DS on cell proliferation was examined by plate clone formation assay and CCK8 assay; the effect of DS on cell migration ability was examined by scratch assay; the effect of DS on cell invasion ability was examined by Transwell invasion assay; the effect of DS on apoptosis rate was examined by flow cytometry; the effect of DS on apoptosis protein (Bax, Bcl-2) expression was verified by Western Blot. Results: The results of CCK8 cell proliferation assay showed that tumor cell proliferation was significantly reduced in the experimental group (0.2%, 0.4%, 0.6%, 0.8% DS) compared with the control group(P < 0.05); the results of clone formation assay showed that tumor cell colony formation was significantly reduced in the experimental group (0.8% DS) compared with the control group (P < 0.05); the results of the scratch assay showed that the scratch healing rate was significantly lower in the experimental group (0.8% DS) compared with the control group (P < 0.05); the results of the Transwell invasion assay showed that the cell invasion ability was significantly lower in the experimental group (0.8% DS) compared with the control group (P < 0.05); the results of flow cytometry showed that the cell apoptosis rate was significantly higher in the experimental group (0.8% DS) compared with the control group (P < 0.05); the results of Western Blot showed that the expression level of apoptotic protein Bax increased, the expression level of anti-apoptotic protein Bcl-2 decreased significantly (P < 0.05) and the Bax/Bcl-2 ratio increased significantly in the experimental group (0.8% DS) compared with the control group (P < 0.05). Conclusion: DS can inhibit human endometrial cancer cells (HEC-1A, Ishikawa) proliferation, migration and invasion, and promote apoptosis.
文章引用：冯楠竹, 张裕民, 李稳, 殷苏威, 郭丽, 张萍. 硫酸右旋糖苷对子宫内膜癌细胞生物学行为的影响[J]. 临床医学进展, 2022, 12(2): 810-819. https://doi.org/10.12677/ACM.2022.122118

参考文献

[1] Siegel, R.L., Miller, K.D., Fuchs, H.E. and Jemal, A. (2021) Cancer Statistics, 2021. CA: A Cancer Journal for Clinicians, 71, 7-33. [Google Scholar] [CrossRef] [PubMed]
[2] Chen, W., Zheng, R., Baade, P.D., Zhang, S., Zeng, H., Bray, F., et al. (2016) Cancer Statistics in China, 2015. CA: A Cancer Journal for Clinicians, 66, 115-132. [Google Scholar] [CrossRef] [PubMed]
[3] Pfeffer, C.M. and Singh, A.T.K. (2018) Apoptosis: A Target for Anticancer Therapy. International Journal of Molecular Sciences, 19, Article No. 448. [Google Scholar] [CrossRef] [PubMed]
[4] 郭嘉欣, 李梦琪, 尚静, 焦龙杏, 侯绍章, 徐远义, 等. 硫酸右旋糖苷通过下调血管内皮生长因子/血管内皮生长因子受体2表达和M2型巨噬细胞浸润抑制胃癌血管生成的研究[J]. 实用医学杂志, 2020, 36(17): 2365-2370.
[5] Takagi, T., Sakakura, C., Kin, S., Nakase, Y., Fukuda, K., Shimomura, K., et al. (2005) Dextran Sulfate Suppresses Cell Adhesion and Cell Cycle Progression of Melanoma Cells. Anticancer Research, 25, 895-902.
[6] Xu, Y., Jin, X., Huang, Y., Wang, J., Wang, X. and Wang, H. (2018) Dextran Sulfate Inhibition on Human Gastric Cancer Cells Invasion, Migration and Epithelial-Mesenchymal Transformation. Oncology Letters, 16, 5041-5049. [Google Scholar] [CrossRef] [PubMed]
[7] Xu, Y., Jin, X., Huang, Y., Dong, J., Wang, H., Wang, X., et al. (2016) Inhibition of Peritoneal Metastasis of Human Gastric Cancer Cells by Dextran Sulphate through the Reduction in HIF-1α and ITGβ1 Expression. Oncology Reports, 35, 2624-2634. [Google Scholar] [CrossRef] [PubMed]
[8] 王文莙,曹相玫,马艳梅, 杨媛媛, 徐远义, 黄允宁. 硫酸右旋糖苷对人胃癌MGC-803细胞增殖和凋亡的影响[J]. 天津医药, 2019, 47(6): 605-608+674.
[9] 李稳, 张裕民, 谭雪莹, 宗军宁, 张萍. 硫酸右旋糖酐对卵巢癌细胞A2780增殖和迁移及侵袭机制研究[J]. 中华肿瘤防治杂志, 2021, 28(8): 583-591.
[10] 朱婷, 张裕民, 鹿恩邦, 殷苏威, 刘欣悦, 张萍. 硫酸右旋糖苷对宫颈癌细胞迁移、侵袭的影响及其分子机制[J]. 山东医药, 2021, 61(26): 30-33.
[11] Tülüce, Y., Lak, P.T.A., Koyuncu, İ., Kılıç, A., Durgun, M. and Özkol, H. (2017) The Apoptotic, Cytotoxic and Genotoxic Effect of Novel Binuclear Boron-Fluoride Complex on Endometrial Cancer. BioMetals, 30, 933-944. [Google Scholar] [CrossRef] [PubMed]
[12] Lheureux, S. and Oza, A.M. (2016) Endometrial Cancer-Targeted Therapies Myth or Reality? Review of Current Targeted Treatments. European Journal of Cancer, 59, 99-108. [Google Scholar] [CrossRef] [PubMed]
[13] 马艳梅, 王潇飞, 王文莙, 杨媛媛, 徐远义, 黄允宁, 等. 硫酸右旋糖酐通过影响TGF-β/Smad4信号通路抑制人胃癌细胞的迁移和侵袭[J]. 实用医学杂志, 2019, 35(1): 35-41.
[14] Burke, P.J. (2017) Mitochondria, Bioenergetics and Apoptosis in Cancer. Trends in Cancer, 3, 857-870. [Google Scholar] [CrossRef] [PubMed]
[15] Campbell, K.J. and Tait, S.W.G. (2018) Targeting BCL-2 Regulated Apoptosis in Cancer. Open Biology, 8, Article ID: 180002. [Google Scholar] [CrossRef] [PubMed]
[16] Hu, L., Chen, M., Chen, X., Zhao, C., Fang, Z., Wang, H., et al. (2020) Chemotherapy-Induced Pyroptosis Is Mediated by BAK/BAX-caspase-3-GSDME Pathway and Inhibited by 2-Bromopalmitate. Cell Death & Disease, 11, Article No. 281. [Google Scholar] [CrossRef] [PubMed]
[17] Delbridge, A.R.D., Grabow, S., Strasser, A. and Vaux, D.L. (2016) Thirty Years of BCL-2: Translating Cell Death Discoveries into Novel Cancer Therapies. Nature Reviews Cancer, 16, 99-109. [Google Scholar] [CrossRef] [PubMed]
[18] 郭倩, 綦春蕾. 子宫内膜癌中细胞凋亡和相关基因的表达研究[J]. 中国肿瘤临床与康复, 2021, 28(8): 905-909.
[19] Jiang, H., Zhao, P.-J., Su, D., Feng, J. and Ma, S.L. (2014) Paris Saponin I Induces Apoptosis via Increasing the Bax/Bcl-2 Ratio and Caspase-3 Expression in Gefitinib-Resistant Non-Small Cell Lung Cancer in Vitro and in Vivo. Molecular Medicine Reports, 9, 2265-2272. [Google Scholar] [CrossRef] [PubMed]
[20] 冯海利, 侯亮. Smac、Bcl-2、Survivin和Bax在早期子宫内膜癌中的表达与预后的相关性分析[J]. 中国妇幼保健, 2016, 31(20): 4275-4279.
[21] Mirakhor, S.S., Ezazi, B.T., Zarghampour, M., Merat, S. and Fouladi, D.F. (2018) Expression of p53, Bcl-2 and Bax in Endometrial Carcinoma, Endometrial Hyperplasia and Normal Endometrium: A Histopathological Study. Journal of Obstetrics and Gynaecology, 38, 999-1004. [Google Scholar] [CrossRef] [PubMed]

为你推荐