Objective To investigate the effect of DRAM1 on the acute ischemic injury of H9C2 cardiomyocytes. Methods H9C2 cardiomyocytes were treated with Oxygen-glucose deprivation (OGD) after DRAM1 adenovirus transfection. MTT assay was performed to detect cell viability and Annex V/PI staining was used to analyze the cell apoptosis. Western blot was performed to measure the expression of P62. Results DRAM1 overexpression increased the H9C2 cardiomycytes viability after OGD treatment for 12 hours. DRAM1 overexpression was attenuated, while siRNA-AD-DRAM1 exacerbated the apoptosis rate of H9C2 cardiomycytes after OGD treatment for 12 hours by Annex V/PI staining. P62 protein expression was increased in the H9C2 cardiomycytes after OGD treatment for 12 hours, which was reversed by DRAM1 overexpression. Conclusion DRAM1 may protect H9C2 cardiomycytes against OGD injury due to the improvement of the autophagy flux.

Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy . However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors P-gp inhibition. Moreover, Western blot experiments revealed that inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying of multiple mechanisms to reverse MDR in lung cancer.