二仙汤化裁方治疗肾虚瘀阻型前列腺癌骨转移临床疗效与药理学研究

Clinical Efficacy and Pharmacology Research of Modified Erxian Decoction(二仙汤化裁方)in the Treatment of Bone Metastasis of Prostate Cancer Patients with Kidney Deficiency and Stasis Syndrome

目的探讨二仙汤化裁方用于治疗肾虚瘀阻型前列腺癌伴骨转移的临床疗效、物质基础及作用机制。方法78例肾虚瘀阻型前列腺癌伴骨转移患者分为西医治疗组(全雄激素阻断治疗)和联合治疗组(加用二仙汤化裁方),服药8周后观察患者的临床疗效及中医症状积分,检测并比较患者治疗前后血清碱性磷酸酶(ALP)水平、视觉模拟疼痛评分(VAS)评定患者的骨转移疼痛情况。依托网络药理学研究检索筛选二仙汤化裁方的有效成分和作用靶标,预测其对前列腺癌骨转移的作用机制。结果治疗8周后联合治疗组较西医治疗组客观缓解率(62.5%vs27.5%)及疾病控制率(78.9%vs 39.5%)均更高。联合治疗组较西医治疗组中医症状改善更显著(13.7±6.2)分vs(8.2±5.7)分。患者的血清ALP水平、VAS较治疗前显著降低。网络药理学研究共筛得二仙汤化裁方117个活性成分及219个不同作用靶标,前列腺癌骨转移3648个疾病作用靶标,方药与疾病重合靶标162个,基因本体(GO)及京都基因与基因组百科全书(KEGG)富集分析预测出与疾病相关的多条作用通路。结论二仙汤化裁方是治疗肾虚瘀阻型前列腺癌骨转移的有效方剂,能有效改善患者临床症状。该研究预测得到二仙汤化裁方治疗痰瘀互结型前列腺癌骨转移的活性成分主要为黄酮类化合物,主要调节靶标是AKT1、MAPK1、RELA、CCND1、CDKN1A,可能通过作用于卡波西肉瘤相关疱疹病毒感染、人巨细胞病毒感染、PI3K-Akt、Th17细胞分化等信号通路等对前列腺癌骨转移起到治疗作用。

Objective To explore the clinical effect,material basis and mechanism of Modified Erxian Decoction(二仙汤化裁方)in the treatment of bone metastasis of prostate cancer patients with kidney deficiency and stasis syndrome. Methods 78 patients with bone metastasis of prostate cancer of kidney deficiency and stasis syndrome were given mechanism of Erxian Decoction were divided into two groups. Western medicine treatment group:total androgen block therapy was given;Combined treatment group:total androgen block therapy combined with Modified Erxian Decoction was given. 8 weeks later to observe the clinical efficacy and TCM symptom score,to detect and compare the serum alkaline phosphatase(ALP)level of the patients before and after taking the medicine. VAS was used to evaluate the pain of bone metastasis. The active ingredients and targets of mechanism of Erxian Decoction by some other components were screened through network pharmacological research,and the mechanism of action of its adjuvant therapy for bone metastasis of prostate cancer was predicted. Results After 8 weeks of treatment,the objective remission rate(62.5% vs 27.5%)and disease control rate(78.9% vs 39.5%)of the combined treatment group were higher than those of Western medicine treatment group. The improvement of TCM symptoms in the combined treatment group was more significant than that in the Western medicine treatment group[(13.7±6.2)vs(8.2±5.7)points]. The level of ALP in serum and the VAS was significantly lower than that before treatment. The network pharmacology research screened 117 active components and 219 different targets of Modified Erxian Decoction,3648 disease targets of bone metastasis of prostate cancer,162 overlapping targets of prescription and disease,and the enrichment analysis of go and KEGG predicted multiple action pathways related to disease. Conclusion Modified Erxian Decoction is an effective prescription for the treatment of bone metastasis of prostate cancer with with kidney deficiency and stasis syndrome,which can effectively improve the clinical symptoms of patients. This study predicts that the main active components of Modified Erxian Decoction in the treatment of bone metastasis of prostate cancer are mainly flavonoids,the main regulatory targets are AKT1,MAPK1,RELA,CCND1,CDKN1 A,which might be related to Kaposi sarcoma-associated herpesvirus infection,human cytomegalovirus infection,PI3 KAkt,Th17 cell differentiation and so on signal pathway plays a therapeutic role in bone metastasis of prostate cancer.