吉马酮调控JAK2/STAT3信号通路对卵巢癌SKOV3细胞增殖、迁移、侵袭的影响

何超月; 任黔川

doi:10.3969/j.issn.2095-5227.2021.08.015

吉马酮调控JAK2/STAT3信号通路对卵巢癌SKOV3细胞增殖、迁移、侵袭的影响

Effect of JAK2/STAT3 signaling pathway regulated by Germacrone on cell viability of ovarian cancer SKOV3

摘要

摘要:
背景卵巢癌死亡率居于女性生殖系统恶性肿瘤的首位，仍需不断探索新的药物来改善其预后，近年来许多研究报道了吉马酮有抗肿瘤细胞作用。
目的探讨吉马酮对人卵巢癌SKOV3细胞增殖、迁移、侵袭能力的影响及其作用机制。
方法培养人卵巢癌SKOV3细胞，分别用0 μmol/L、70 μmol/L、140 μmol/L、210 μmol/L、280 μmol/L、350 μmol/L吉马酮作用于卵巢癌SKOV3细胞24 h、48 h、72 h，采用CCK-8法检测吉马酮对卵巢癌SKOV3细胞增殖能力的影响；采用细胞划痕实验及Transwell实验观察吉马酮对卵巢癌细胞迁移、侵袭能力的影响；Western blot法检测各组细胞JAK2/STAT3信号通路相关蛋白及肿瘤侵袭转移相关蛋白MMP2、MMP9的表达。
结果 CCK-8实验结果提示吉马酮可以抑制人卵巢SKOV3细胞的增殖，并存在时间及浓度依赖性；细胞划痕实验显示0 μmol/L、140 μmol/L、280 μmol/L吉马酮组划痕愈合率分别为69.00% ± 6.76%、40.33% ± 5.21%、13.79% ± 9.23% (P＜0.05)；Transwell迁移实验显示0 μmol/L、140 μmol/L、280 μmol/L吉马酮组穿过小室细胞个数分别为466.5 ± 47.7、319.4 ± 41.2、149.7 ± 26.3(P＜0.05)；Transwell侵袭实验显示0 μmol/L、140 μmol/L、280 μmol/L吉马酮组穿过小室细胞个数分别为278.6 ± 71.8、161.0 ± 35.4、70.1 ± 24.9。与对照组相比，药物组对细胞迁移及侵袭有明显的抑制作用(P＜0.05)，并具有浓度依赖性；Western blot结果提示吉马酮可浓度依赖性下调p-JAK2、p-STAT3蛋白表达，降低p-JAK2/JAK2、p-STAT3/STAT3，还可浓度依赖性下调MMP2、MMP9蛋白表达(P＜0.05)。
结论吉马酮可明显抑制卵巢癌SKOV3细胞的增殖、迁移、侵袭能力，其机制可能与下调JAK2/STAT3信号通路活性、下调MMP2、MMP9蛋白表达有关。

Abstract:
Background The mortality of ovarian cancer ranks the first among female reproductive malignancies, and new drugs need to be explored to improve its prognosis. In recent years, many studies have reported germacrone has anti-tumor effect.
Objective To investigate the effect of germacrone on the proliferation, migration and invasion of ovarian cancer SKOV3 cells and explore its mechanism.
Methods Human ovarian cancer SKOV3 cells were cultured and treated with germacrone at 0, 70, 140, 210, 280 and 350 μmol/L for 24 h, 48 h and 72 h, respectively. The effect of germacrone on the proliferation of ovarian cancer SKOV3 cells was detected by CCK-8 assay. Cell scratch assay and Transwell assay were used to observe the effect of germacrone on the migration and invasion ability of ovarian cancer SKOV3 cells. The expressions of JAK2/STAT3 signaling pathway related proteins and tumor invasion and metastasis related proteins MMP2 and MMP9 in each group were detected by Western Blot.
Results CCK-8 assay showed that germacrone could inhibit the proliferation of SKOV3 cells in a concentration- and time-dependent manner. Cell scratch assay showed that the scratch healing rate of 0 μmol/L, 140 μmol/L, 280 μmol/L germacrone groups were 69.00% ± 6.76%, 40.33% ± 5.21%, 13.79% ± 9.23%, respectively. Transwell migration experiment showed that the number of cells passing through the chamber in 0 μmol/L, 140 μmol/L, 280 μmol/L germacrone groups were 466.5 ± 47.7, 319.4 ± 41.2, 149.7 ± 26.3, respectively. Transwell invasion experiment showed that the number of cells passing through the chamber in 0 μmol/L, 140 mmol/L, 280 mmol/L germacrone groups were 278.6 ± 71.7, 161.0 ± 35.4, 70.1 ± 24.9, respectively. Compared to control group, germacrone groups inhibited the migration and invasion of SKOV3 cells significantly in a concentration-dependent manner (P＜0.05). Western blot results showed that germacrone could dose-dependently down-regulate the protein expressions of p-JAK2 and p-STAT3, decrease p-JAK2/JAK2 and p-STAT3/STAT3, and down-regulate the protein expressions of MMP2 and MMP9 (P＜0.05).
Conclusion Germacrone could inhibit the proliferation, migration and invasion of ovarian cancer SKOV3 cells, and its mechanism may be related to the down-regulation of the activity of JAK2/STAT3 signaling pathway and down-regulation of the expressions of MMP2 and MMP9 protein.

HTML全文

参考文献(22)

施引文献

资源附件(0)