目的:观察黄芪总皂苷对小鼠结肠癌肝转移的抑制作用,并探讨其通过调节Wnt3a/β-catenin/EMT通路发挥抑制作用的相关机制。方法:用CT26.WT细胞构建结肠癌原位移植瘤小鼠模型,将50只BA L B/c小鼠随机分为假手术组、模型组、阳性对照组、...目的:观察黄芪总皂苷对小鼠结肠癌肝转移的抑制作用,并探讨其通过调节Wnt3a/β-catenin/EMT通路发挥抑制作用的相关机制。方法:用CT26.WT细胞构建结肠癌原位移植瘤小鼠模型,将50只BA L B/c小鼠随机分为假手术组、模型组、阳性对照组、黄芪总皂苷低剂量组(50 m g·k g^(-1)·d^(-1))、黄芪总皂苷高剂量组(100 mg·kg^(-1)·d^(-1)),每组10只。取各组小鼠肝脏组织,观察结肠肿瘤肝转移情况,采用HE染色观察肝组织病理形态学变化,Western Blot检测Wnt3a/β-catenin/EMT相关蛋白的表达,免疫荧光染色检测β-catenin蛋白在肝组织中的表达情况。结果:模型组小鼠肝脏出现明显转移结节,且病理变化较明显,尤其出现较多肿瘤细胞浸润情况。与模型组比较,黄芪总皂苷高剂量组及阳性对照组小鼠肝组织转移灶数量明显减少,肝脏病理得到明显改善,肿瘤细胞浸润明显减少,肝组织中Wnt3a、β-catenin、N-cadherin、Vimentin蛋白表达量显著降低(P<0.05,P<0.01),GSK3β和E-cadherin蛋白表达量显著升高(P<0.05)。结论:黄芪总皂苷可能通过调控肝组织中Wnt3a/β-catenin/EMT信号通路发挥抑制结肠癌原位移植瘤小鼠肝转移的作用。展开更多
We report two cases of solitary mediastinal lymph node recurrence after colon cancer resection. Both cases had para-aortic lymph node metastasis at the time of initial surgery and received adjuvant chemotherapy for 4 ...We report two cases of solitary mediastinal lymph node recurrence after colon cancer resection. Both cases had para-aortic lymph node metastasis at the time of initial surgery and received adjuvant chemotherapy for 4 years in case 1 and 18 mo in case 2. The time to recurrence was more than 8 years in both cases. After resection of the recurrent tumor, the patient is doing well with no recurrence for 6 years in case 1 and 4 mo in case 2. Patients should be followed up after colon cancer surgery considering the possibility of solitary mediastinal lymph node recurrence if they had para-aortic node metastasis at the time of initial surgery.展开更多
Multidrug resistance(MDR)develops during chemotherapy in nearly all colorectal cancerpatients.It is envisaged that reversal of MDR plays a pivotal role in the success of chemotherapy.This study investigated thepotenti...Multidrug resistance(MDR)develops during chemotherapy in nearly all colorectal cancerpatients.It is envisaged that reversal of MDR plays a pivotal role in the success of chemotherapy.This study investigated thepotential pharmacological action in reversing MDR in colon cancer cells by the two most potent tanshinones,namely cryptotanshinone and dihydrotanshinone.They targeted two common MDR mechanisms,including overexpression of P-glycoprotein(P-gp)and suppression of apoptosis.Using a bi-directional transport assay,the two tanshinones decreased P-gp-mediated digoxin effluxin Caco-2 cells.They also potentiated the cytotoxicities of doxorubicin and irinotecan in P-gp overexpressing SW620Ad300 cells via increased intracellular accumulation of both anti-cancer drugs,as a result of down-regulation of P-gp mRNA and protein levels as well as inhibition of P-gp ATPase activity.In addition,the level of apoptosis was also found to be relatively suppressed in SW620Ad300 cells as compared with the parental SW620 cells.Interestingly,although cryptotanshinone and dihydrotanshinone induced less apoptosis in SW620Ad300 cells as compared to their parental cells,they produced more autophagic cell death in these MDR cells.In this regard,the drug resistant SW620Ad300 cells were more prone to cell death in response to the anti-cancer action of thetwo tanshinones.Furthermore,the cytotoxic action of the two tanshinones was shown to be p53-independent,further demonstrated theirunique anti-cancer activities in overcoming drug resistance due to the reduction of p53 expression together with a decrease of apoptosis in colon cancer cells.Taken together,the current findings indicate a great potential for cryptotanshinone and dihydrotanshinone against MDR colon cancer cells,in spite of P-gp overexpression and suppression of apoptosis.They are promising candidates to be developed as therapeutic agents and/or as an adjuvant therapy for colorectal cancer,especially for patients with MDR cancer types.展开更多
文摘目的:观察黄芪总皂苷对小鼠结肠癌肝转移的抑制作用,并探讨其通过调节Wnt3a/β-catenin/EMT通路发挥抑制作用的相关机制。方法:用CT26.WT细胞构建结肠癌原位移植瘤小鼠模型,将50只BA L B/c小鼠随机分为假手术组、模型组、阳性对照组、黄芪总皂苷低剂量组(50 m g·k g^(-1)·d^(-1))、黄芪总皂苷高剂量组(100 mg·kg^(-1)·d^(-1)),每组10只。取各组小鼠肝脏组织,观察结肠肿瘤肝转移情况,采用HE染色观察肝组织病理形态学变化,Western Blot检测Wnt3a/β-catenin/EMT相关蛋白的表达,免疫荧光染色检测β-catenin蛋白在肝组织中的表达情况。结果:模型组小鼠肝脏出现明显转移结节,且病理变化较明显,尤其出现较多肿瘤细胞浸润情况。与模型组比较,黄芪总皂苷高剂量组及阳性对照组小鼠肝组织转移灶数量明显减少,肝脏病理得到明显改善,肿瘤细胞浸润明显减少,肝组织中Wnt3a、β-catenin、N-cadherin、Vimentin蛋白表达量显著降低(P<0.05,P<0.01),GSK3β和E-cadherin蛋白表达量显著升高(P<0.05)。结论:黄芪总皂苷可能通过调控肝组织中Wnt3a/β-catenin/EMT信号通路发挥抑制结肠癌原位移植瘤小鼠肝转移的作用。
基金Supported by Department of Surgery,Osaka Medical Center for Cancer and Cardiovascular Disease,Osaka 537-8511,Japan
文摘We report two cases of solitary mediastinal lymph node recurrence after colon cancer resection. Both cases had para-aortic lymph node metastasis at the time of initial surgery and received adjuvant chemotherapy for 4 years in case 1 and 18 mo in case 2. The time to recurrence was more than 8 years in both cases. After resection of the recurrent tumor, the patient is doing well with no recurrence for 6 years in case 1 and 4 mo in case 2. Patients should be followed up after colon cancer surgery considering the possibility of solitary mediastinal lymph node recurrence if they had para-aortic node metastasis at the time of initial surgery.
基金The project supported by the Hong Kong Research Grants Council and the Innovation Technology Commission
文摘Multidrug resistance(MDR)develops during chemotherapy in nearly all colorectal cancerpatients.It is envisaged that reversal of MDR plays a pivotal role in the success of chemotherapy.This study investigated thepotential pharmacological action in reversing MDR in colon cancer cells by the two most potent tanshinones,namely cryptotanshinone and dihydrotanshinone.They targeted two common MDR mechanisms,including overexpression of P-glycoprotein(P-gp)and suppression of apoptosis.Using a bi-directional transport assay,the two tanshinones decreased P-gp-mediated digoxin effluxin Caco-2 cells.They also potentiated the cytotoxicities of doxorubicin and irinotecan in P-gp overexpressing SW620Ad300 cells via increased intracellular accumulation of both anti-cancer drugs,as a result of down-regulation of P-gp mRNA and protein levels as well as inhibition of P-gp ATPase activity.In addition,the level of apoptosis was also found to be relatively suppressed in SW620Ad300 cells as compared with the parental SW620 cells.Interestingly,although cryptotanshinone and dihydrotanshinone induced less apoptosis in SW620Ad300 cells as compared to their parental cells,they produced more autophagic cell death in these MDR cells.In this regard,the drug resistant SW620Ad300 cells were more prone to cell death in response to the anti-cancer action of thetwo tanshinones.Furthermore,the cytotoxic action of the two tanshinones was shown to be p53-independent,further demonstrated theirunique anti-cancer activities in overcoming drug resistance due to the reduction of p53 expression together with a decrease of apoptosis in colon cancer cells.Taken together,the current findings indicate a great potential for cryptotanshinone and dihydrotanshinone against MDR colon cancer cells,in spite of P-gp overexpression and suppression of apoptosis.They are promising candidates to be developed as therapeutic agents and/or as an adjuvant therapy for colorectal cancer,especially for patients with MDR cancer types.
