Abstract：
OBJECTIVE: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer.
METHODS: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo.
RESULTS: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G0/G1 phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05).
CONCLUSIONS: Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.
METHODS: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo.
RESULTS: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G0/G1 phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05).
CONCLUSIONS: Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.
摘要：
目的：观察黄芩苷对结肠癌的治疗作用及其机制。
方法：黄芩苷对结肠癌细胞MC38和CT26增殖和生长的影响。通过网络药理学观察并研究黄芩苷治疗结肠癌的潜在分子靶点。此外，进行分子对接和药物亲和响应靶标稳定性（DARTS）分析以确认潜在靶标与黄芩苷之间的相互作用。最后,通过计算机模拟分析预测的机制已在体外和体内进行了实验验证。
结果：黄芩苷显著抑制增殖，入侵,迁移,诱导MC38和CT26细胞凋亡(P均<0.01)。此外,黄芩苷导致细胞周期停滞在S期，而在细胞的微小部分检测到G0/G1期。随后的网络药理学分析确定了与黄芩苷相关的6个治疗靶点，这可能会影响各种途径，包括39个生物过程和99个信号通路。此外,分子对接和DARTS预测黄芩苷与细胞周期蛋白依赖性激酶抑制剂2A（CDKN2A）的潜在结合，蛋白激酶B（AKT），caspase3和丝裂原活化蛋白激酶（MAPK）。体外，CDKN2A的表达式，MAPK,黄芩苷抑制MC38和CT26细胞中的p-AKT。在体内,黄芩苷通过使p-AKT失活,显著降低结肠癌小鼠模型的肿瘤体积和重量(均P<0.01),CDKN2A,细胞周期蛋白依赖性激酶4,细胞周期蛋白依赖性激酶2,白细胞介素-1,肿瘤坏死因子α,并激活胱天蛋白酶3和小鼠双分2同源信号(均P<0.05)。
结论：黄芩苷通过抑制CDKN2A蛋白水平对结肠癌有预防作用，可作为结肠癌的治疗靶点。
方法：黄芩苷对结肠癌细胞MC38和CT26增殖和生长的影响。通过网络药理学观察并研究黄芩苷治疗结肠癌的潜在分子靶点。此外，进行分子对接和药物亲和响应靶标稳定性（DARTS）分析以确认潜在靶标与黄芩苷之间的相互作用。最后,通过计算机模拟分析预测的机制已在体外和体内进行了实验验证。
结果：黄芩苷显著抑制增殖，入侵,迁移,诱导MC38和CT26细胞凋亡(P均<0.01)。此外,黄芩苷导致细胞周期停滞在S期，而在细胞的微小部分检测到G0/G1期。随后的网络药理学分析确定了与黄芩苷相关的6个治疗靶点，这可能会影响各种途径，包括39个生物过程和99个信号通路。此外,分子对接和DARTS预测黄芩苷与细胞周期蛋白依赖性激酶抑制剂2A（CDKN2A）的潜在结合，蛋白激酶B（AKT），caspase3和丝裂原活化蛋白激酶（MAPK）。体外，CDKN2A的表达式，MAPK,黄芩苷抑制MC38和CT26细胞中的p-AKT。在体内,黄芩苷通过使p-AKT失活,显著降低结肠癌小鼠模型的肿瘤体积和重量(均P<0.01),CDKN2A,细胞周期蛋白依赖性激酶4,细胞周期蛋白依赖性激酶2,白细胞介素-1,肿瘤坏死因子α,并激活胱天蛋白酶3和小鼠双分2同源信号(均P<0.05)。
结论：黄芩苷通过抑制CDKN2A蛋白水平对结肠癌有预防作用，可作为结肠癌的治疗靶点。
