The Effect Of Glutaminase Inhibitor-968on Cell Cycle And It’s Combining Use With Erlotinib

Malignant tumor is the most serious disease in china especially the breast cancer,it is a serious threat to people’s health, what’s more, its incidence and mortality ratesare high. Although with advances in detection methods, there are still a considerablenumber of patients in the late stage even though we can diagnose it in the early time.Therefore, systemic chemotherapy plays an important role in the comprehensivetreatment of cancer. In addition, chemotherapy either as the main treatment for cancer,or as a supplement of surgery and radiotherapy can prolong survival and quality oflife of cancer patients with great help. Especially the implementation of neoadjuvantchemotherapy can make people re-surgery again when they lost the opportunities.therefore the chemical treatment of cancer has been a hot topic, especially someefficacy, toxic side effects of new chemotherapy drugs.In order to invent these cancer drugs, we need to solve it in a totally new way,maybe tumor metabolism will be the breakthrough: cancer can change the way ofmetabolic to meet their needs of the energy and biosynthesis compared with normalcells, There are two aspects: one is Warburg effect, in this case, even with enoughoxygen, cancer cells will convert glucose into pyruvate to produce ATP, but thischange will affect acid cycle, such that cells do not have enough material for thesynthesis of biological macromolecules, in order to compensate for this loss, tumorcells has a second metabolic change which is in taking a large number of glutamineand convert it into α-ketoglutarate to complement the TCA cycle, maintainingbiosynthetic requirements. Therefore, how to inhibit the key rate-limiting enzyme ofglutamine metabolism has become a hot topic. Drugs which can specific inhibit thisenzyme can have a decisive role in cancer treatment.968is a small molecule drug of that kind, it can specifically inhibit glutaminase,restrain glutamine convert into glutamate, impede tumor cells macromolecularmetabolism, tumor cells due to the "hunger" and death. From the Previous studies, wefound that cell cycle can be severely affected in the presence of968. As a continuousprocess, any one phase block of cell cycle can lead to stagnation of cell growth ordeath. Therefore, to further study which genes related to cell cycle is affected by968,has a great significance to understand the mechanism. In this research, we found that968can decrease tumor cells expressing EGFR,which present dose-dependent trend, whether968can combined with EGFRinhibitors to exhibit synergistic effect and a better efficacy, will be our future researchfocus.As a new drug We does not studied It’s mechanism in-depth, so to further studyits effects on tumor cell growth and reliable screening therapeutic targets will be thefocus of our study.Based on the above considerations, we use968as the primary study drug andbreast cancer MDA-MB231, MCF-7, lung cancer HCC827as the research object, Tofurther identify the mechanism of968on cell cycle, cell growth and it’s combined usewith Erlotinib.