奥拉帕利联合热灌注化疗调控JAK2/STAT3信号通路抑制卵巢癌血管新生及转移的机制研究

Mechanism of olapalil combined with thermoperfusion chemotherapy to regulate JAK2/STAT3 signaling pathway and inhibit angiogenesis and metastasis of ovarian cancer

目的探讨奥拉帕利联合热灌注化疗方案治疗卵巢癌的临床疗效,分析其对血管新生、转移的影响及其可能的作用机制。方法选取2019年8月至2021年8月收治的105例卵巢癌患者为研究对象,随机数字表法分为对照组(n=52)和观察组(n=53),分别给予热灌注化疗和热灌注化疗联合奥拉帕利治疗。统计2组临床疗效、不良反应和预后情况。比较2组治疗前后Janus激酶2/信号转导子和转录激活子3(JAK2/STAT3)信号通路相关指标[JAK2、STAT3、血管内皮生长因子(VEGF)、环氧合酶-2(COX-2)、Twist相关蛋白1(Twist1)、基质金属蛋白酶2(MMP-2)]、Treg/Th17细胞、肿瘤标志物[癌胚抗原(CEA)、B7同源体4(B7-H4)、绒毛膜促性腺激素β亚单位(β-HCG)]的水平。结果观察组疾病控制率高于对照组(P<0.05);观察组治疗2个周期后、4个周期后JAK2 mRNA、STAT3 mRNA、Twist1 mRNA、VEGF、COX-2、MMP-2及Treg、Th17细胞的水平低于对照组,Treg/Th17高于对照组(P<0.05);观察组治疗2个周期后、4个周期后外周血CEA、B7-H4、β-HCG水平低于对照组(P<0.05);2组不良反应发生率、生存率比较,差异无统计学意义(P>0.05);观察组中位无进展生存期长于对照组(P<0.05)。结论奥拉帕利联合热灌注化疗方案治疗卵巢癌的疗效显著,且具有一定安全性,可抑制血管新生、血管生成拟态形成,降低其转移能力,并可调节免疫功能,延长生存期,其机制可能与抑制JAK2/STAT3信号通路活化有关。

AIM To investigate the clinical efficacy of olapalil combined with thermoperfusion chemotherapy in the treatment of ovarian cancer,and to analyze the effect on angiogenesis and metastasis and the possible mechanism of action.METHODS A total of 105 patients with ovarian cancer admitted to our hospital from August 2019 to August 2021 were selected as the study subjects,and randomly divided into control group(n=52)and observation group(n=53).They were given hyperthermic chemotherapy or hyperthermic chemotherapy combined with orapalil,respectively.The clinical efficacy,toxicity and side effects and prognosis of the 2 groups were analyzed.Janus kinase 2/signal transductor and transcriptional activator 3(JAK2/STAT3)signal path-related indexes[JAK2,STAT3,vascular endothelial growth factor(VEGF),cyclooxygenase-2(COX-2),Twist-related protein 1(Twist1),matrix metalloproteinase 2(MMP-2)],Treg/Th17 cells,tumor markers(CEA),B7 homologue 4(B7-H4),chorionic gonadotropinβsubunit(β-hCG)levels before and after treatment in 2 groups were compared.RESULTS The disease control rate of observation group was higher than that of control group(P<0.05).After 2 and 4 cycles,the expressions of JAK2 mRNA,STAT3 mRNA,Twist1 mRNA,VEGF,COX-2,MMP-2 and Treg and Th17 cells in the observation group were lower than those in the control group,and the expressions of Treg/Th17 cells were higher than those in the control group(P<0.05).The levels of CEA,B7-H4 andβ-HCG in peripheral blood of the observation group were lower than those of the control group after 2 and 4 cycles of treatment(P<0.05).There was no significant difference in the incidence and survival rate of toxic and side effects between the 2 groups(P>0.05).The median progression-free survival between the two groups was statistically significant(P<0.05).CONCLUSION Olaparil combined with thermoperfusion chemotherapy is effective and safe in the treatment of ovarian cancer.It can inhibit angiogenesis and the formation of angiogenic mimicry,reduce the metastasis ability,regulate immune function and prolong survival,which may be related to the inhibition of the activation of JAK2/STAT3 signaling pathway.