Mechanisms adopted by cancer cells to escape apoptosis–A review

Inactivation of apoptosis is the prime phenomenon in cancer development and cancer treatments.Mutations in the apoptotic pathway not only exert resistance to apoptosis and provide a survival advantage to cancer cells but also confer resistance to cancer therapies.Escaping apoptosis is the“hallmark”of cancer cells.Cancer cells can withstand many apoptotic stimuli,such as DNA damage,unfavorable environments,and cytotoxic therapies.Substantial research has been carried out and is in good progress on the various mechanisms adopted by cancer cells to evade apoptosis.This article reviews the apoptosis escape mechanisms by cancer cells,viz.apoptotic gene alterations(in few essential and accessory apoptotic genes),post-translational modifications(phosphorylation and ubiquitination of apoptotic proteins),metabolic alterations,mitochondrial alterations,immunity escape,epigenetics,cancer cell dormancy,cancer clonal theory,and reversibility of apoptosis.The review reveals that there is a wide scope for further research to address the various challenges in realizing successful cancer therapies that involve reversing the apoptotic resistance and/or inducing apoptosis in tumor cells.

Intestinal ischemia and reperfusion induced second impairment of the rat heart

Objective: To study the changes of oxygen free radical, expression of apoptotic gene, ultrastructure of myocardial cell and second injury of the heart following the intestinal ischemia and reperfusion. Methods: Making the models of ischemia and reperfusion by clamping superior mesenteric artery, the concentration of NO and SOD in the blood was examined before clamping the artery and reperfusion for 0, 30, 60 min, 1, 3, and 7 d. The expression of Bax, Bal-2, and p53 in myocardial cell was studied by means of immunohistochemical SP method and the microstructure damage was observed under electron microscopy. Results: After clamping the superior mesenteric artery and reperfusion the concentration of NO increased continuously and reached a peak for reperfusion 7 d (P<0.01) but that of SOD decreased from 30 min to 7 d. The expression of Bax, p53 and Bcl-2 also increased obviously especially for reperfusion 30 min and 7 d following ischemia and reperfusion. After reperfusion for 30 min the positive cell rate of Bax, p53 and Bcl-2 was 53.6%, 45.9% and 67.9%, for reperfusion 7 d it was 52.4%, 43.4% and 31.9% respectively, but the positive cell rate of Bax and p53 was higher than that of Bcl-2. The result of electron microscopy observation showed mfofiliments breaked, dissolved and chromatin condensed. Conclusion: Intestinal ischemia and reperfusion of rat can induced the changes of oxygen free radical and the expression of apoptotic gene and second injury of myocardial cells.

Probe into Reverse Operation of Apoptosis Gene

Objective:The programmed death process of cells according to gene coding belongs to apoptotic natural extinction(PCD).The purpose of this study is to explore the phenomenon of“returning to old age and rejuvenating children”in the extreme anoxia,no nutrients and survival in the extreme environment of fish and earthworm.Methods:the adult earthworms were put into the sealed quartz sand or fine yellow sand plastic bottle with humidity of 35-40%70 ml and poured out 100-150 d,then put back into the natural environment(simulated natural plastic basin)and raised 100-150 d,to collect the experimental information.The same object can be observed repeatedly.Results:The earthworms which were closed in the little oxygen-free and nutrition-deficient vials were reduced by autophagy,and the rings and reproductive pores disappeared completely.When they were put back into the natural environment for two or three months,they were all restored to their original morphological structure.Conclusion:Most of the same subjects underwent 1-3 years of cyclic observation.The biological structure was adapted to the changing environment.It was helped by the resonance of many biota and complex stress factors.

Effects of Inotodiol Extracts from Inonotus Obliquus on Proliferation Cycle and Apoptotic Gene of Human Lung Adenocarcinoma Cell Line A549

Objective： To observe the proliferation inhibition, apoptosis, and cell proliferation cycle of human lung carcinoma cell line A549 treated with Inotodiol extracts from Inonotus obliquus and explore the possibility of Inotodiol extracts from Inonotus obliquus as a new tumor chemopreventive drug. Methods： Human lung cancer cell line A549 was treated with different concentrations of Inotodiol, the effects of Inotodiol on cell apoptosis, the expression of Ki-67, Bcl-2, Bax, and p53 and cell cycle were detected by TUNEL assay, immunohistochemistry, and flow cytometry assay respectively. Results： Inotodiol extracts had antiproliferation effect on human lung carcinoma cell line A549. The expression of Ki-67 decreased with the increase of Inotodiol concentration and exposure time （P〈0.05）, in a close-dependent and time-dependent manner. The typical characteristics of the apoptosis of A549 cells treated with Inotodiol were observed, and the apoptotic rate of A549 cell at 48 h was the highest by TUNEL assay. Inotodiol arrested A549 cells in the S phase, and apoptotic peak was observed by flow cytometry. Immunocytochemistry indicated that the expression of Bcl-2 protein decreased, while the expression of p53 and Bax proteins increased in A549 cells treated with Inotodiol, compared with the control cells （P〈0.05）. Conclusion： Inotodiol can inhibit proliferation and induce the apoptosis of A549 cells, and its molecular mechanism may be associated with the up-regulating expression of p53 and bax proteins and down- regulating expression of Bcl-2 protein, which arrested A549 cells in S phase.