Chemosensitivity to doxorubicin in primary cells derived from tumor of FVB/N‑Trp53tm1Hw1 with TALEN‑mediated Trp53 mutant gene
10.1186/s42826-023-00175-2
- Author:
Woobin YUN
1
;
Ji Eun KIM
;
You Jeong JIN
;
Yu Jeong ROH
;
Hee Jin SONG
;
Ayun SEOL
;
Tae Ryeol KIM
;
Kyeong Seon MIN
;
Eun Seo PARK
;
Gi Ho PARK
;
Hyun Gu KANG
;
Yeon Shik CHOI
;
Dae Youn HWANG
Author Information
1. Department of Biomaterials Science (BK21 FOUR Program)/Life and Industry Convergence Research Institute, College of Natural Resources & Life Science, Pusan National University, Miryang 50463, Korea
- Publication Type:RESEARCH
- From:Laboratory Animal Research
2023;39(4):287-297
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background:To evaluate the chemosensitivity to doxorubicin (DOX) in two primary cells derived from a tumor of FVB/N-Trp53tm1Hw1 knockout (KO) mice with TALEN-mediated Trp53 mutant gene, we evaluated the cell survivability, cell cycle distribution, apoptotic cell numbers and apoptotic protein expression in solid tumor cells and ascetic tumor cells treated with DOX.
Results:The primary tumor cells showed a significant (P < 0.05) defect for UV-induced upregulation of the Trp53 pro-tein, and consisted of different ratios of leukocytes, fibroblasts, epithelial cells and mesenchymal cells. The IC50 level to DOX was lower in both primary cells (IC50 = 0.12 μM and 0.20 μM) as compared to the CT26 cells (IC50 = 0.32 μM), although the solid tumor was more sensitive. Also, the number of cells arrested at the G0/G1 stage was significantly decreased (24.7–23.1% in primary tumor cells treated with DOX, P < 0.05) while arrest at the G2 stage was enhanced to 296.8–254.3% in DOX-treated primary tumor cells compared with DOX-treated CT26 cells. Furthermore, apoptotic cells of early and late stage were greatly increased in the two primary cell-lines treated with DOX when compared to same conditions for CT26 cells. However, the Bax/Bcl-2 expression level was maintained constant in the primary tumor and CT26 cells.
Conclusions:To the best of our knowledge, these results are the first to successfully detect an alteration in chemosensitivity to DOX in solid tumor cells and ascetic tumor cells derived from tumor of FVB/N-Trp53tm1Hw1 mice TALENmediated Trp53 mutant gene.
