Cisplatin Induced The Apoptosis Of Glioma Through Mitochondria And Endoplasmic Reticulum Apoptosis Signaling Pathway

Background: Glioblastoma is the most aggressive and the most frequent common tumor,comprising approximately50%of the cerebral gliomas. Surgical removal of the tumor is thefirst-line therapy. Unfortunately, these tumor cells are highly mobile and usually infiltrate thesurrounding tissues. Therefore, surgery has to be followed by chemotherapy and radiationtherapy to further reduce the number of remaining tumor cells. At present, the research of themost commonly used and effective anti-tumor medicine CDDP treat glioma is less, and thetreatment mechanism is not very clear.There have endogenous apoptosis and exogenous apoptosis pathways. And intrinsicapoptotic pathway is the most commonly studied apoptotic pathways. The intrinsic apoptoticpathway also known as mitochondrial apoptosis, Caspases and Bcl-2family proteins involvedin intrinsic apoptotic. Early apoptosis, mitochondrial membrane permeability transition poreopen, the membrane permeability increase mitochondrial membrane potential decrease,release apoptosis related factors, such as cytochrome C (CytC) and apoptosis inducing factor(AIF) to the cytoplasm. Cytochrome C can bind with the apoptotic protease activating factor1in the cytoplasm, recruit Caspase-9and form the apoptotic bodies, so that the Caspase-9activation and activating Caspase3, activation of Caspase3can specially cleave the substrate,eventually lead to apoptosis. When there is extracellular stimuli, promoting apoptosis proteinBax that exists in cytoplasm migrated to the mitochondrial outer membrane, form theheterologous dimers, cause mitochondrial membrane permeability increase, resulting incytochrome C release, leading to cell apoptosis.When there is extracellular stimuli, there have endoplasmic reticulum stress. And theactivation of unfolding protein response relieve the stress, especially the high expression ofCHOP in UPR reaction activation can induce apoptosis related to endoplasmic reticulumstress response pathways, at present is mainly as iconic-apoptosis protein of endoplasmicreticulum stress.CDDP is a traditional chemotherapeutic drugs, and the treatment mechanism in thetreatment of glioma is still unknown, mitochondrial apoptosis signaling pathway and endoplasmic reticulum stress-apoptosis signaling pathway may be involved.Objective: Research whether CDDP induced the apoptosis of glioma throughmitochondria and endoplasmic reticulum apoptosis signaling pathways.Method: Culture T98G and U251cells in vitro, detect the effect of differentconcentration CDDP on the growth of two cells for24h by MTT. And detect the effect ofdifferent concentration CDDP on the expression levels of apoptosis related proteins CleavedCaspase-3and Cleaved PARP, mitochondrial apoptosis related proteins Cytochrome C, Bcl-2and Bax, endoplasmic reticulum stress-apoptosis related proteins GRP78and CHOP.Result:1.CDDP can obviously inhibit the growth of T98G and U251in dose-dependentmanner.2. The different concertation CDDP can notably increase the expression levels ofapoptosis related proteins Cleaved Caspase-3and Cleaved PARP in T98G and U251cells.3. The different concertation CDDP can notably increase the expression levels ofmitochondrial apoptosis related proteins cytochrome C and Bax, at the same time, decreasethe expression levels of anti-apoptosis protein Bcl-2in T98G and U251cells.4. The different concertation CDDP can notably increase the expression levels ofendoplasmic reticulum stress-apoptosis related proteins GRP78and CHOP in T98G and U251cells.Conclusion: CDDP can induce the apoptosis of glioma through mitochondria andendoplasmic reticulum apoptosis signaling pathways.