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二氢色原酮拼接多环吡咯螺环氧化吲哚类化合物3m抗皮肤鳞状细胞癌的作用及机制
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| 篇名： | 二氢色原酮拼接多环吡咯螺环氧化吲哚类化合物3m抗皮肤鳞状细胞癌的作用及机制 |
| TITLE： | Anti-cutaneous squamous cell carcinoma effect and mechanism of dihydrochromone-spliced polycyclic pyrrole-spiroepoxidole compound 3m |
| 摘要： | 目的 探究二氢色原酮拼接多环吡咯螺环氧化吲哚类化合物3m抗皮肤鳞状细胞癌的作用及机制。方法以人皮肤鳞状细胞癌A431、Colo-16细胞为研究对象，采用CCK-8法检测不同浓度（5、10、20、40、80μmol/L）3m作用24、48、72h后对A431、Colo-16细胞增殖的影响，并计算培养48h时的半数抑制浓度（IC50）。将A431、Colo-16细胞分别分为对照组和3m低、高浓度组（15、30μmol/L），加入相应药物或培养基培养48h后，采用倒置显微镜观察细胞形态变化，检测细胞克隆形成率、迁移率、侵袭数、细胞周期分布和凋亡率，检测细胞中Janus激酶2/信号转导及转录激活因子3（JAK2/STAT3）信号通路相关蛋白[JAK2、STAT3、B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）]磷酸化或表达水平及其mRNA的表达水平。结果不同浓度3m作用24、48、72h后均能显著抑制A431、Colo-16细胞增殖（P＜0.01），48h时的IC50分别为20.36、23.72μmol/L。作用48h后，与对照组比较，3m低、高浓度组A431、Colo-16细胞排列稀疏、连接松散；克隆形成率、迁移率、侵袭数，细胞中JAK2、STAT3、Bcl-2mRNA表达水平，JAK2、STAT3蛋白磷酸化水平和Bcl-2蛋白表达水平均显著降低/减少（P＜0.01）；细胞周期G2期占比、凋亡率、Bax蛋白和mRNA表达水平均显著升高（P＜0.01）；上述作用均呈剂量依赖性。结论3m可呈剂量依赖性地抑制皮肤鳞状细胞癌A431、Colo-16细胞的增殖、克隆形成、迁移、侵袭能力，其作用机制与抑制JAK2/STAT3信号通路活性，诱导细胞凋亡有关。 |
| ABSTRACT： | OBJECTIVE To study the effect and mechanism of dihydrochromone-spliced polycyclic pyrrole-spiroepoxidole compound 3m on cutaneous squamous cell carcinoma. METHODS Using human cutaneous squamous cell carcinoma A431 and Colo-16 cells as research subjects， CCK-8 assay was used to detect the effects of different concentrations of 3m （5， 10， 20， 40， 80 μmol/L） on the proliferation of A431 and Colo-16 cells after 24， 48 and 72 hours； the median inhibitory concentration （IC50） was calculated at 48 h of treatment. A431 and Colo-16 cells were divided into control group， 3m low-concentration and high- concentration groups （15， 30 μmol/L）. After treated with relevant drugs or culture medium for 48 h， the morphological changes of cells in each group were observed by inverted microscope. Clone formation rate， migration rate and number of cell invasions， cell cycle distribution and apoptosis rate were detected. The phosphorylation， or expression of Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway related proteins [JAK2， STAT3， B-cell lymphocyte-2 （Bcl-2）， Bcl-2- associated X protein （Bax）]， and their mRNA expression in cells were detected. RESULTS 3m could significantly inhibit the proliferation of A431 and Colo-16 cells after treated for 24， 48， 72 h （P＜0.01）， and IC50 of them were 20.36， 23.72 μmol/L， respectively. After 48 hours of treatment， compared with control group， A431 and Colo-16 cells arranged sparsely and loosely connected in 3m low-concentration and high-concentration groups. The clone formation rate， migration rate， number of cell invasions， mRNA expressions of JAK2， STAT3 and Bcl-2， the phosphorylation of JAK2 and STAT3， protein expression of Bcl-2 were significantly decreased/weakened （P＜0.01）. Proportion of cell cycle in G2 phase， apoptosis rate， protein and mRNA expression of Bax were increased significantly （P＜0.01）； and all the above effects were in dose-dependent manner. CONCLUSIONS 3m can inhibit the proliferation， clone formation， migration and invasion abilities of cutaneous squamous cell carcinoma A431 and Colo-16 cells in a dose-dependent manner， the mechanism of which may be associated with inhibiting the activity of JAK2/STAT3 signaling pathway， and inducing cell apoptosis. |
| 期刊： | 2023年第34卷第09期 |
| 作者： | 唐姗姗；荣冬芸；王叶；苏羽屾；汪涛；龙秋；曹煜 |
| AUTHORS： | TANG Shanshan，RONG Dongyun，WANG Ye，SU Yushen，WANG Tao，LONG Qiu，CAO Yu |
| 关键字： | 皮肤鳞状细胞癌；二氢色原酮；多环吡咯螺环氧化吲哚；增殖；凋亡；迁移；侵袭 |
| KEYWORDS： | cutaneous squamous cell carcinoma； dihydrochromone； polycyclic pyrrole-spiroepoxidole； proliferation； |
| 阅读数： | 117 次 |
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