Inhibition of human 67-kDa laminin receptor sensitizes multidrug resistance colon cancer cell line SW480 for apoptosis induction

Abstract

The adhesion mediated drug resistance in cancer cells resulted from adhesion of the extracellular matrix is a major cause for multidrug resistance (MDR) and leads chemotherapeutic failure for colon cancer. In this study, we explored the role of 67-kDa laminin receptor (67LR) in chemotherapeutic drug resistance in colon cancer cells. SiRNA-mediated knockdown of 67LR decreased the cell adhesion when laminins were applied. Moreover, 67LR knockdown increased the expression of pro-apoptotic gene Bax but inhibited the expression of anti-apoptotic gene Bcl-2. Enhanced apoptosis was observed in 67LR siRNA-transfected SW480 cell when the cell was treated with doxorubicin for apoptosis induction. Furthermore, MTT assay revealed that the IC50 of chemotherapeutic toward SW480 cell adhesion to laminins was reduced after 67LR knockdown, indicating there was a significant increase of drug sensitivity in SW480 cell. In conclusion, our study demonstrated that 67LR plays a considerable role in the development of colon cancer MDR.

(−)-Epigallocatechin-3-gallate (EGCG) attenuates salt-induced hypertension and renal injury in Dahl salt-sensitive rats

“…Although 67LR has been well studied in various tumour cells 20,21 , few studies on its expression in the kidney have been conducted. In this study, we found that 67LR was expressed in the epithelial cells of the proximal tubules, the epithelial cells of the renal capsules, podocytes, vascular endothelial cells, and fibroblasts in the kidney.…”

“…The reduction in 67LR expression might have been due to the role of 67LR in the pathology of renal injury. 67LR is reported to be a molecular marker of metastatic aggressiveness 20,21 . Renal epithelial cells could be transformed to the mesenchymal cell phenotype and acquire the ability to migrate and invade, which could promote the development of renal fibrosis 38 .…”

“…www.nature.com/scientificreports www.nature.com/scientificreports/ The non-integrin cell surface receptor, 67-kDa laminin receptor (67LR) is highly expressed on the surfaces of various tumour cells and is widely recognized as a molecular marker of metastatic aggressiveness 20,21 . Moreover, 67LR is a membrane receptor of EGCG 22 , and the binding of EGCG to the 67LR protein reportedly mediates many of EGCG's beneficial activities, such as its anti-proliferative and apoptosis-inducing effects on multiple tumour cells 23 , antioxidant effects 24,25 , and anti-inflammatory activities 26,27 .…”

Knock-Down of LRP/LR Influences Signalling Pathways in Late Stage Colorectal Carcinoma Cells

“…S4). The apoptotic induction observed is suggested to be due to the reduced interaction of LRP/LR with focal adhesion kinase (FAK) [52,56]. In particular, a study performed by Lu et al (2016) demonstrated that siRNA-mediated knock-down of LRP/LR reduced FAK phosphorylation, leading to the knock-down of the anti-apoptotic protein Bcl-2 and an up-regulation of the pro-apoptotic Bax protein, reiterating that the knock-down of LRP/LR induces apoptosis [56].…”

“…The apoptotic induction observed is suggested to be due to the reduced interaction of LRP/LR with focal adhesion kinase (FAK) [52,56]. In particular, a study performed by Lu et al (2016) demonstrated that siRNA-mediated knock-down of LRP/LR reduced FAK phosphorylation, leading to the knock-down of the anti-apoptotic protein Bcl-2 and an up-regulation of the pro-apoptotic Bax protein, reiterating that the knock-down of LRP/LR induces apoptosis [56]. Moreover, another study performed by Sun et al (2014) showed that the LRP/LR-laminin-1 interaction may allow for LRP/LR's interaction with FAK, leading to the activation of the PI3-kinase/AKT and MEK/ERK 1/2 cellular survival pathways as well as an increased expression of the Bcl-2 protein [52].…”