We have located links that may give you full text access.
The mechanism study of lentiviral vector carrying methioninase enhances the sensitivity of drug-resistant gastric cancer cells to Cisplatin.
British Journal of Cancer 2018 May
BACKGROUND: To investigate the mechanism of lentiviral vector carrying methioninase enhances the sensitivity of drug-resistant gastric cancer cells to Cisplatin.
METHODS: Death receptors, anti-apoptotic protein, NF-κB, and TRAIL pathway-related factors were detected. The influence of LV-METase transfection on cell viability and pathway-related proteins were assessed by MTT method and western blot, respectively. Different treatments (NF-κB or caspase-3 inhibitor induction, TRAIL supplement, etc.) were performed in gastric cancer cells and the above parameters were analysed. Moreover, the connection between miR-21 and NF-κB or caspase-8 was determined by Chip and luciferase assay, respectively. LV-METase transfection drug-resistant gastric cancer cells were injected subcutaneously into mice.
RESULTS: The expression of free MET, miR-21-5p, MDR1, P-gp, and DR5 was significantly increased in drug-resistant gastric cancer cell lines. When cells were transfected with LV-METase, intracellular TRAIL signalling was activated while NF-κB pathway was inhibited. Besides, enhanced TRAIL signalling or repressed NF-κB pathway can promote the sensitivity of drug-resistant strains to Cisplatin, and the combination shows more sensitive to sensitisation. LV-METase promoted TRAIL expression by reducing NF-κB, thereby contributing to the downregulation of P-gp and enhancing the susceptibility of drug-resistant gastric cancer cells to Cisplatin. Furthermore, miR-21 regulated by NF-κB mediated the expression of P-gp protein via inhibiting caspase-8, thus regulating Cisplatin-induced cell death.
CONCLUSIONS: Our results suggest that LV-METase has potential as a therapeutic agent for gastric cancer treatment.
METHODS: Death receptors, anti-apoptotic protein, NF-κB, and TRAIL pathway-related factors were detected. The influence of LV-METase transfection on cell viability and pathway-related proteins were assessed by MTT method and western blot, respectively. Different treatments (NF-κB or caspase-3 inhibitor induction, TRAIL supplement, etc.) were performed in gastric cancer cells and the above parameters were analysed. Moreover, the connection between miR-21 and NF-κB or caspase-8 was determined by Chip and luciferase assay, respectively. LV-METase transfection drug-resistant gastric cancer cells were injected subcutaneously into mice.
RESULTS: The expression of free MET, miR-21-5p, MDR1, P-gp, and DR5 was significantly increased in drug-resistant gastric cancer cell lines. When cells were transfected with LV-METase, intracellular TRAIL signalling was activated while NF-κB pathway was inhibited. Besides, enhanced TRAIL signalling or repressed NF-κB pathway can promote the sensitivity of drug-resistant strains to Cisplatin, and the combination shows more sensitive to sensitisation. LV-METase promoted TRAIL expression by reducing NF-κB, thereby contributing to the downregulation of P-gp and enhancing the susceptibility of drug-resistant gastric cancer cells to Cisplatin. Furthermore, miR-21 regulated by NF-κB mediated the expression of P-gp protein via inhibiting caspase-8, thus regulating Cisplatin-induced cell death.
CONCLUSIONS: Our results suggest that LV-METase has potential as a therapeutic agent for gastric cancer treatment.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app