Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells

Objective: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer(CRC) through network pharmacology and molecular docking combined with experimental verification. Methods: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. Results: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase(Akt1, Akt2), cyclin-dependent kinase 6(CDK6), matrix metalloproteinase-9(MMP9), epidermal growth factor receptor(EGFR), cell division control protein 42 homolog(CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets(Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein(P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G_1–S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9(P<0.05), and might play an anticancer role through Akt signaling pathway. Conclusions: Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

气血方、养阴方、健脾方联合化疗预防高危Ⅱ期及Ⅲ期结直肠癌术后复发转移多中心随机对照研究

目的:观察气血方、养阴方、健脾方对高危Ⅱ期及Ⅲ期结直肠癌术后患者复发转移的影响。方法:采用多中心随机对照方法,选择高危Ⅱ期及Ⅲ期结直肠癌术后患者303例按照2∶1的比例随机分为试验组202例及对照组101例,两组均接受4~9个周期奥沙利铂联合卡培他滨(CapeOx)方案辅助化疗,试验组根据证型加用气血方、养阴方、健脾方,观察两组1、2、5年无病生存率(DFS)、卡氏评分(KPS)、中医证候积分和不良反应。结果:最终纳入281例患者,随机分配至试验组190例,对照组91例。经过48个月的中位随访时间,试验组中74例(38.9%)出现复发,对照组中40例(44.0%)出现了复发,试验组1、2、5年DFS分别为94.2%(179/190)、84.2%(160/190)、61.1%(116/190),优于对照组的91.2%(83/91)、81.3%(74/91)、56.0%(51/91)。亚组分析中,试验组阴虚证患者干预后5年DFS差异有统计学意义(P=0.037)。两组不良反应总发生率差异无统计学意义,试验组的恶心/呕吐等消化道不良反应发生率显著低于对照组(P=0.014)。结论:气血方、养阴方、健脾方联合化疗可降低高危Ⅱ期及Ⅲ期结直肠癌术后患者复发转移风险,阴虚证患者是应用中医药抗结直肠癌术后复发转移的潜在优势人群。

结直肠癌切除联合射频消融对同时性结直肠癌肝转移临床指标、安全性及预后的影响

目的探讨结直肠癌切除联合射频消融治疗同时性结直肠癌肝转移对相关临床指标、患者的安全性及预后生存率的影响,为该疗法在临床的应用提供依据。方法回顾性分析2011年1月—2013年12月间绍兴市中心医院收治的同时性结直肠癌肝转移患者48例,根据治疗方法分为观察组和对照组,其中对照组26例接受根治性手术切除结直肠癌变和肝转移部位,观察组22例接受结直肠癌切除联合射频消融。采用t检验比较2组的临床相关指标、并发症发生情况,应用Kaplan-Meier法绘制生存曲线,并采用Log rank检验比较2组患者的预后。结果治疗后2组患者的谷丙转氨酶(ALT)和谷草转氨酶(AST)均明显升高,血清白蛋白(ALB)和胆碱酯酶(CHE)均不同程度的降低,而且术后3 d和7 d观察组患者对ALT、AST、ALB和CHE的改善程度均显著大于对照组,以上差异均有统计学意义(P<0.05)。2组的并发症发生率差异无统计学意义(P>0.05)。观察组无进展生存率显著高于对照组,HR=0.420,95%CI:0.131~0.971,P=0.025,而观察组总体生存率与对照组相近,HR=1.623,95%CI:0.748~3.519,P=0.190。结论结直肠癌切除和射频消融联合治疗能减少对肝脏功能的损伤,虽然总体生存率与手术切除相比差异无统计学意义,但该疗法为无法进行肝转移灶切除的患者提供了新的治疗方案,具有一定的临床应用价值。