Expression of GAB1 in ER-positive breast cancer and its effect on MCF-7 cells’ metastasis / 西安交通大学学报(医学版)

【Objective】 To evaluate the expression of GAB1 in ER-positive breast cancer and its effect on MCF-7 cells’ metastasis. 【Methods】 The expression of GAB1 in ER-positive breast cancer tissues was detected by immunohistochemistry. We analyzed the relationship of GAB1 expression with the patients’ clinicopathological features and prognosis. The invasion and metastasis abilities of MCF-7 cells after silencing GAB1 expression were observed by Transwell assay. The effect of GAB1 expression on the EMT of breast cancer cells was analyzed by Western blotting. 【Results】 Immunohistochemical staining showed that GAB1 expression had significant correlation with lymph node metastasis(P=0.014) and stage(P=0.011). Transwell results showed that shGAB1 significantly inhibited the migration and invasion of human breast cancer MCF-7 cells. Western blotting results showed that shGAB1 significantly increased E-cadherin expression and decreased Vimentin expression. Kaplan-Meier analysis revealed that ER-positive breast cancer patients with high GAB1 expression tumors had a significantly worse relapse-free survival rate than those with low GAB1 expression tumors(P<0.001). Multivariate analysis showed that stage and GAB1 expression were independent predictors of survival. 【Conclusion】 GAB1 is highly expressed in ER-positive breast cancer. ShGAB1 expression can inhibit the migration, invasion and EMT of breast cancer cells. GAB1 might be used as one of the valuable markers for prognosis in patients with ER-positive breast cancer.

Andrographolide is an Alternative Treatment to Overcome Resistance in ER-Positive Breast Cancer via Cholesterol Biosynthesis Pathway

@#Oestrogen receptor (ER)-positive breast cancer is one of the common forms of breast cancer affecting women worldwide. ER-positive breast cancer patients are subjected to antioestrogen therapy such as selective oestrogen receptor modulator (SERM) and aromatase inhibitors (AIs). Recently, the emergence of resistance to anti-oestrogen treatment is under intensive focus. The different mechanisms postulated to explain the occurrence of resistance in ER-positive breast cancer treatment include the loss of ER function and the crosstalk between signalling pathways in cancer cells. Recent literature highlighted that the cholesterol biosynthesis pathway acts as a novel mechanism underlying resistance to oestrogen deprivation. The present study aimed to highlight the role of cholesterol biosynthesis in anti-oestrogen treatment resistance, putatively suggesting an alternative plant-based treatment using andrographolide from Andrographis paniculata. The hypolipidaemic effect of andrographolide can be utilised to prevent the resistance in the treatment of ER-positive breast cancer contributed by cholesterol biosynthesis.

Effects of combination treatment with SAHA and TRAIL on ER positive breast cancer cell MCF-7 / 中国药理学通报

Aim To investigate the effects of com-bined treatment of SAHA and TRAIL on human breast cancer ER positive cell line MCF-7 . Methods MCF-7 cells were treated with SAHA and/or TRAIL. The inhibitory rates were detected by real-time cell prolifer-ation assays. Morphology changes of MCF-7 cells were observed through time-lapse live cell imaging acquisi-tion. Results Real-time cell proliferation assays showed that the anti-tumor efficacy of SAHA was sig-nificantly enhanced in combination with TRAIL. The results of time-lapse live cell imaging acquisition dem-onstrated that, with treatment of SAHA and TRAIL, the growth inhibition of MCF-7 cells was more obvious than that of in TRAIL or SAHA treatment alone. Con-clusion The combination treatment of SAHA and TRAIL has a synergistic effect of growth inhibition on breast cancer MCF-7 cells.

Combining anticancer effect of tamoxifen and ?-interferon on breast cancer in vitro and its mechanism / 中国普通外科杂志

Objective To investigate the combining anticancer effect of tamoxifen(TAM) and ?-interferon on breast cancer cells in vitro and its mechanism.Methods MCF-7 ER-positive breast cancer cell lines were treated with tamoxifen alone,or in combination with ?-interferon and/or estrogen in vitro.Cell proliferation was evaluated by MTT assay;FCM was used to determine the distribution of cell cycle,cell apoptosis and protein expression of Bcl-2,Bax,Fas,FasL,Caspase-8,and the activity of Caspase-3.Results TAM inhibited the proliferation of ER-postive breast cancer cells with cell cycle arrest in G0/G1 phase and with induction of apoptosis,and the proliferation-promoting effect of estrogen on MCF-7 was blocked by TAM.Anticancer effect of TAM was enhanced when cells were pretreated with ?-interferon for 24 hours.Bcl-2 protein expression was down-regulated and Caspase-8 was up-regulated by TAM and/or ?-interferon,but these drugs did not affect Bax,Fas,FasL protein expression and the activity of Caspase-3.Conclusions TAM has anticancer effect by inhibiting proliferation and inducing apoptosis in ER-positive breast cancer cells in vitro,and ?-interferon can enhance anticancer effect of TAM on breast cancer cells.The mechanism of these effects may be related with the down-regulation of Bcl-2 expression and up-regulation of Caspase-8 by TAM and ?-interferon.