ASPH Regulates Chemosensitivity Of Human Cervical Cancer Cells To Cisplatin Through P53 Pathway

The incidence and mortality of cervical cancer ranks fourth among female tumors.Although the incidence of cervical cancer has declined with the application of cervical cancer screening and HPV vaccine,the incidence of cervical cancer in women aged 2039 is globally And the mortality rate is rising,cervical cancer is still a major problem threatening the lives and health of women around the world.Currently,cervical cancer treatment includes surgery or concurrent radiotherapy and chemotherapy.However,most advanced patients have metastasized and developed drug resistance,and their five-year survival rate is less than 20%.Therefore,it is very necessary to find new therapeutic targets.Aspartate-β-hydroxylase is highly expressed in liver cancer,cholangiocarcinoma,pancreatic cancer,breast cancer and other malignant tumors,and participates in a variety of biological functions,such as proliferation,migration,aging,etc.,suggesting that ASPH may be an anti Targets for cancer treatment.At present,there are no related reports on the occurrence and development of ASPH and cervical cancer.In this study,we mainly discussed the function and mechanism of ASPH in regulating the chemotherapy sensitivity of cervical cancer cells to cisplatin.Through the database and tissue chip,it is found that ASPH is highly expressed in cervical cancer and low in normal cervical tissues;pathological sections further prove that ASPH is low-expression in normal tissues,elevated in precancerous tissues,and expressed in invasive cervical cancer Further rise.Knockdown ASPH can increase the sensitivity of HeLa cells to cisplatin,and increase the cisplatin-induced apoptosis,cell cycle G2/M phase arrest,and ROS generation.Up-regulating ASPH can reduce the chemosensitivity of SiHa cells to cisplatin.ASPH affects cisplatin chemotherapy sensitivity by regulating DNA damage and p53 expression.Inhibition of p53 activity can partially eliminate the effect of ASPH on cisplatin chemotherapy sensitivity.In summary,this paper confirms that down-regulation of ASPH enhances the chemotherapy sensitivity of cervical cancer cells to cisplatin by increasing p53 transcriptional activity and DNA damage response,indicating that ASPH can be used as a new target for the treatment of cervical cancer.