ABSTRACT
AIM:To explore the molecular mechanism through which curcumin reverses hepatocyte growth factor (HGF)-induced resistance to gefitinib in lung cancer cells.METHODS:The methods of MTT assay, wound healing assay and Western blot were used to observe the effects of HGF, curcumin and gefitinib on the migration, drug susceptibility, epithelial-mesenchymal transition, and related signaling pathways in the PC9 lung cancer cells.RESULTS:HGF reduced susceptibility of the PC9 cells to gefitinib, and curcumin significantly reversed HGF-induced resistance to gefitinib.HGF induced migration and epihelial-mesenchymal transition, and promoted c-Met/AKT/mTOR pathway activation in the PC9 cells.Gefitinib alone did not prevent the above activities.However, combined with curcumin, gefitinib prevented the above activities.CONCLUSION:Curcumin reverses HGF-induced resistance of the PC9 cells to gefitinib by preventing epithelial-mesenchymal transition and inhibiting c-Met/AKT/mTOR activation.
ABSTRACT
Objective:To investigate the role of STAT3 in the pathogenesis of acute viral myocarditis(VCM)in mice and its possible mechanism.Methods:Acute VCM mice models were established forty-five mice were randomly divided into blind control group (n=10),virus-infection control group(n=15),RPMintervention group(n=20).In RPM intervention group,RPM was given to mice intraperitoneally once a day with general dosage of 0.4 mg(/kg?d)at 24 hours before infected with coxsackie virus B3,mice of virus-infection control group were given the same volume of Dulbcco's Modifed Eagle Medium and virus.Blind control group was only given the same volume of Dulbcco's Modifed Eagle Medium,but not infected coxsackie virus B3.Twelve days later,the general condition and survival rate of mice were observed and then all experimental mice were sacrificed patholog and detecting CVB3 virus titer in myocardium. And double-sandwich ELISA was used to detect the levels of IFN-?,and TNF-?in the serum.Results:The pathological changes of myocardium of the mice in RPM intervention displayed more seriously than the mice with acute VMC and both the cytokines expressions in the serum of RPM intervention group were higher than those of the acute VMC group,but there was no significant difference in the virus titer between the two groups.Conclusions:The activation of STAT3 can somehow protect myocardial tissues during the incidence of viral myocarditis in mice to inhibit its activation and improve the sensibility of mice to CVB3,although the activation of STAT3 cannot affect CVB3 virus replication,it can inhibit the over-expression of IFN-?and TNF-?to weaken myocardial damage.