Inducing apoptosis and enhancing chemosensitivity to Gemcitabine via RNA interference targeting Mcl-1 gene in pancreatic carcinoma cell

Abstract

Our data suggests that the specific downregulation of Mcl-1 by RNAi is a promising approach to induce apoptosis and enhance the chemosensitivity for pancreatic carcinoma gene therapy.

Cationic Liposomal Co-delivery of Small Interfering RNA and a MEK Inhibitor for Enhanced Anticancer Efficacy

“…Mcl1-specific siRNA (siMcl1) is known to enhance the sensitivity of cancer cells to anticancer chemotherapeutics, and a previous study has shown that cancer cells overexpressing Mcl1 are less sensitive to the apoptosis-inducing effects of chemotherapeutic agents (17). Consistent with this, a combination chemogene regimen including siMcl1 was reported to enhance the chemosensitivity of pancreatic carcinoma to gemcitabine (18). Moreover, co-treatment with siMcl1 was shown to increase the chemosensitivity of cisplatin-resistant ovarian carcinoma cells (2).…”

“…Apoptosis-inducing effects have reported for siMcl1 in ovarian carcinoma cells (2), and for antisense Mcl1 oligonucleotides in non-small cell lung cancer cells (17). Moreover, siMcl1 has been shown to enhance the chemosensitivity of pancreatic carcinoma cells to gemcitabine (25). Given these previous reports, the chemosensitizing potential of siMcl1 co-delivered with anticancer drugs would be expected to increase the sensitivity of cancer cells, apart from the apoptosis-inducing effects of siMcl1.…”

Prognostic role of myeloid cell leukemia‐1 protein (Mcl‐1) expression in human gastric cancer

“…Firstly, we showed that the level of Mcl-1 expression was significantly higher in four human gastric cancer cell lines than in normal human [24][25][26]. To our knowledge, there have been no reports about the prognostic significance of Mcl-1 expression in human gastric cancer.…”

Nelfinavir induces mitochondria protection by ERK1/2-mediated mcl-1 stabilization that can be overcome by sorafenib

“…Mcl-1 protein expression is of crucial importance for the integrity of the outer mitochondrial membrane potential. Several studies have shown that siRNA-mediated downregulation of mcl-1 induces or sensitizes cancer cells to apoptosis [25][26][27][28]. The mcl-1 protein has an extraordinarily short half-time of 30 min [26] that can be prolonged or shortened by phosphorylation events, depending on the phosphorylation site [26].…”