Effect of silencing MPZL1 on tumor cell stemness and drug resistance of A549 / Tax cells via β-catenin signaling
10.19405/j.cnki.issn1000-1492.2024.01.016
- Author:
Chao Zang
1
;
Qiao Ge
1
;
Chao Li
1
;
Haining Hong
2
;
Wei Li
3
Author Information
1. Dept of Thoracic Surgery，First Affiliated Hospital，Bengbu Medical College，Bengbu 233004 ; Graduate School，Bengbu Medical College，Bengbu 233030
2. Dept of Thoracic Surgery，Third Affiliated People's Hospital，Bengbu Medical College，Bengbu 233000
3. Dept of Thoracic Surgery，First Affiliated Hospital，Bengbu Medical College，Bengbu 233004
- Publication Type:Journal Article
- Keywords:
MPZL1;
tumor stemness;
A549 / Tax lung cancer cell;
multiple drug resistance;
paclitaxel
- From:
Acta Universitatis Medicinalis Anhui
2024;59(1):99-105
- CountryChina
- Language:Chinese
-
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.
- Full text:202406241709123815沉默MPZL1调控β-ca...ax细胞干性及耐药性的影响_臧超.pdf
