RESUMO
Adriamycin resistance in HCC seriously hinders the treatment of patients, it is necessary to investigate the mechanisms. Autophagy is involved in adriamycin resistance and JNK2 is related to autophagy. However, whether JNK2 inducing drug resistance though autophagy is unknown. GL-V9, a new synthesized flavonoid derivative, has been proved of its anti-tumor effects. The aim of the study is to explore the role of JNK2-related autophagy on adriamycin-induced drug resistance and the effects of GL-V9 on reversing adriamycin resistance. We concluded that JNK2 played an important role in drug resistance induced by adriamycin. The high expression of JNK2 activated protective autophagy in Hep G2-DOXR cells under non-stress condition, which protected cells from drug attacking. Furthermore, we found that GL-V9 reversed adriamycin resistance by blocking the JNK2-related protective autophagy in HCC.
RESUMO
JNK is a key protein in the third stages of MAPK pro-tein kinase activation cascade,and is located in the key node of multiple signal transduction network.It plays a pivotal role in the cell proliferation,differentiation,apoptosis and some other important cell biological processes.Therefore it acts as an im-portant factor in regulating the development of some major human diseases,such as cancer.But the functional diversity and com-plexity of three JNK isoforms in different cell types make it diffi- cult to develop anticancer drugs with JNK as a treatment target. In this review,we summarized the apoptotic signaling network of JNK and the regulation functions of JNK in cell apoptosis and proliferation.We also discuss the different functions of 3 JNK isoforms in human cancer.
RESUMO
Objective To investigate the expression of JNK2 in hyperoxic lung injury ,and explore the protective effect of sub-stance P (SP) on hyperoxic lung injury and its mechanism .Methods Sixteen SD rats were divided into four groups with 4 rats in each group :room-air and f 9 g/L saline group (group A) ,room-air and SP group (group B) ,hyperoxia injury group and f 9 g/L sa-line group (group C) ,hyperoxia injury group and SP group (group D) .Rats ingroup B and D were injected with SP 1 × 10-6 mol · L -1 · kg -1 · d-1 intraperitoneally ,group A and group C were injected with an equal volume of 9 g/L saline .The animals were sac-rificed after 14 days of experiment .Lung pathology was examined with light microscopy ,lung wet/dry (W/D) ratio and the level of SP and PCNA and TUNEL in lung were evaluated .The Superoxide dismutase (SOD) ,malondialdehyde (MDA) and glutathione (GSH) level were assayed respectively in lung tissue .The quanlity of JNK2 protein was detected by Western blot analysis .Results Compared with group A ,the high oxygen groups all had different degrees of lung injury ,,while the lung pathological pictures in group D was improved significantly compared with group C .Western blot showed that level of JNK2 in group C was obviously higher than that of group A ;After the intervention ,level of JNK2 in group D was lower than that of group C .The lung W/D retio , TUNEL and PCNA expression and distribution SOD ,MDA and GSH was consistent with the trends of JNK2 protein expression . Conclusion High oxygen stress can activate damage lung tissue JNK 2 activity ;SP protection mechanism of high oxygen lung injury may be induced by cutting high oxygen activation of JNK 2 to inhibit oxidative damage .