Research On The Mechanism Of Autophagy Influences Tongue Squamous Cancer Tca-8113 Cells’ Sensitivity To Adriamycin

ObjectiveAutophagy is an important way to maintain a stable environment within the cell, the relationship between macrophages and tumor cells, development, prognosis and efficacy are very important. This paper was intended to explore the impact of autophagy to tongue squamous of TCA-8113 cells in chemotherapy. Regulating autophagy and observed the changes of tongue tca-8113 cells about its proliferation and apoptosis after chemotherapy of ADM.Methods1、MTT assay was first to explore the chemotherapy drug doxorubicin(Adriamycin ADM) autophagy inhibitor 3-methyl adenine(3-Methyladeine, 3MA) chloroquine(chloroquine CQ) and autophagy activator rapamycin(Rapamycin RAPA) were used alone for TCA-8113 cells and the proliferation of them, to clarify the dose- response relationship.2、Western blot were used to detected the expression of autophagy-related protein Beclin1, atg5 and lc3 in the separately used with ADM.3、MTT assay was detected the three autophagy regulators about 3-MA, CQ and RAPA were separately combined with ADM then Observed TCA-8113 cells Survival rates.4、Acridine Orange Dyeing and Flow cytometry were used to detected the three autophagy regulators about 3-MA, CQ and RAPA were separately combined with ADM and monotherapy then the TCA-8113 cells’ apoptosis.5、Western blot were used to detected the expression of autophagy-related protein Beclin1, atg5 and lc3 in the three autophagy regulators of 3-MA, CQ and RAPA were separately combined with ADM or monotherapy and the possible autophagy-related pathways major protein p-Akt and p-erk.Results1、ADM could inhibit proliferation of TCA-8113 cells by dose-dependent manners. 3-MA and CQ has certain inhibition on TCA-8113 cells by dose-dependent manners and RAPA has no inhibition on TCA-8113 cells.2、ADM can induce autophagic response.3、Autophagy inhibitor 3-Ma and CQ separately combined with ADM could increase pro-apoptotic effect on TCA-8113 cells and the autophagy activator RAPA combined with ADM can protect TCA-8113 cells to reduce the ADM induced apoptosis of TCA-8113 cells.4 、 ADM can induce autophagic response and then involved in the pro-apoptotic effect of ADM on TCA-8113 cells, possibly through the regulation of ERK pathwaysConclusions1 、 Autophagy as a protective mechanism responses to the apoptosis induced by ADM.2、3-MA or chloroquine could inhibit autophagy that can promote apoptosis induced by doxorubicin TCA-8113. Rapamycin activatior of autophagy may be appropriate to reduce the toxic effects of doxorubicin on TCA-8113 cells.3、3-MA and CQ autophagy inhibitors could inhibit autophagy and enhance the pro-apoptotic effect of ADM on TCA-8113 cells, this process may adjust by Erk pathway.While RAPA activatior of autophagy that participate in the protection of TCA-8113 cells respond to pro-apoptotic effect of ADM and this process may be through Erk pathway regulates.