Associoation Of Mdr1 Gene Methylation Status With Nact Effects Of Cervical Cancer

Objective:Research the correlation between methylation status of cervical cancer tumor cell multidrug resistace gene 1 with the curative effect of cervical cancer,and compare the methylation status between untreated patients and with NACT patients, to ivestigate some sensitive index can predict the clinical effects of multidrug resistence.Methods:Common immunity tissue chemical technology was used to detect the expression level of P-gp which was codogeniced by gene MDR1, MALDI-TOF MassARRY EpiTYPER DNA methylation analyzing technique was used to detect the 30 CPG sites status of mdrl gene promoter region which in groups before and after NACT of cervical cancer and nomal group.Results:(1)The expression level of P-gp is negative of all the normal cervical tissue,The expression level of P-gp is lower of NACT sensitive group (n=31) than the drug resistence group(n=9) (p<0.05);(2) NACT can induce the expression level of P-gp, comparing with the untreated patients, the expression level of P-gp were lower in the patients with NACT(P<0.05);(3)In comparison with NACT sensitive group (n=31), the MDR1 methylation status in drug resistence group (n=9) was lower (p <0.05) on CpG₂,3,4 sites; (4)Comparing with the untreated patients (n=40), the MDR1 methylation status in drug resistence group were lower in the patients with NACT (n=40)on CpG₇,CpG₈,CpG₁2,13,CpG₁8,CpG₁9,20 CpG₂3,CpG₂4 sites (P<0.05); (5)The MDR1 methylation status in cervical cancer group (n=80) were lower than in the nomal group (n=30) on CpG₂,3,4,CpG₅,CpG₆,CpG₇,CpG₈,CpG₉,10,CpG₁2,13,CpG₁8,CpG₁9,20 CpG₂2,CpG₂3,CpG₂4 sites (P<0.05).Conclusions:(1) There is relative correlation between the expression level of P-gp which codogeniced by gene MDR1 with NACT, The expression level of P-gp were higher in drug resistence group than the NACT sensitive group; NACT can induce the expression level of P-gp, the expression level of P-gp were advanced in the patients with NACT comparing with the untreated patients.(2)There is relative correlation between the MDR1 methylation status of multidrug resistance gene 1 in cervical cancer tumor cell with the curative effect of cervical cancer. The MDR1 methylation status in drug resistence group was lower on CpG₂,3,4 site than in NACT sensitive group; the MDR1 methylation status in drug resistence group were lower in the patients with NACT on CpG₇,CpG₈,CpG₁2,13,CpG₁8,CpG₁9,20,CpG₂3,CpG₂4 sites than in untreated patients.(3) The expression level of P-gp are stepping up in normal cervix tissue,untreated cervical cancer tissue and NACT cervical cancer tissue,but the MDR1 methylation status in which are decending,which confirmed they are inverse correlation between the expression level of P-gp and the methylation status of MDR1.