ABSTRACT
Objective @# To explore the effect of MPZL1 knockdown in A549 Taxol resistant (A549 / Tax) cells and whether it affect drug resistance and tumor cell stemness by regulating β-catenin.@*Methods @#A549 and A549 / Tax cells were treated with different concentrations of doxorubicin and paclitaxel to observe the differences in drug resist- ance between the two cells.Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the MP- ZL1 expression level in A549 and A549 / Tax cells. After knockdown or overexpression of MPZL1 in A549 / Tax cells,cells were divided into control group,small hairpin RNA negative control ( sh-NC) group,MPZL1 knock- down(sh-MPZL1) group,overexpression negative control ( OE-NC) group,MPZL1 overexpression ( OE-MPZL1) group.Cell counting kit-8 ( CCK-8 ) and clone formation assay were utilized to investigate cell proliferation and clone formation ablity.Western blot assay was used to detect the protein expression after the cells treated with Wnt / β-catenin signaling inhibitor XAV939 and activator CHIR-99201 . @*Results @# The half inhibitory concentration ( IC50 ) of doxorubicin and paclitaxel in A549 / Tax cells significantly increased compared to A549 cells(P<0. 01) . MPZL1 presented a higher expression trend in A549 / Tax cells.The IC50 values of A549 / Tax for doxorubicin and paclitaxel were 2. 731 mg / ml and 4. 939 μg / ml after MPZL1 knockdown,compared to 4. 541 mg / ml and 13. 55 μg / ml in the NC group (P<0. 01) .The results of CCK-8 and clone formation assay showed that the knockdown of MPZL1 reduced the viability of cells proliferation and clonal formation ability (P<0. 05) .Western blot results in- dicated that the expression levels of MPZL1 protein,tumor cell stemness associated proteins ( CD44,CD133) ,β - catenin and multidrug resistance protein 1 (MDR1) ,lung resistance-related protein ( LRP) were significantly re- duced in the sh-MPZL1 group. Furthermore ,XAV939 could inhibit the expression levels of MPZL1 ,CD44, CD133,MDR1,LRP and β-catenin(P<0. 01) .The inhibitory effect of knockdown MPZL1 on the aforementioned proteins was significantly reversed by CHIR-99201 treatment.@*Conclusion @# MPZL1 is highly expressed in A549 / Tax cells.Knockdown MPZL1 suppresses the tumor cell stemness and proliferation,thereby reversing the drug re- sistance of doxorubicin and paclitaxel in A549 / Tax cells.