Study on synergistic inhibitory effect of ruxolitinib and decitabine on growth of HEL cells with TET2 knockdown
10.3969/j.issn.1001-1978.2021.07.018
- Author:
Li-Xia FU
1
;
Ying-Shao WANG
1
;
Jie BAI
1
;
Fang-Nan XIAO
2
;
Jun-Zhe SONG
2
;
Jiao-Jiao BAI
2
;
Yuan ZHOU
2
Author Information
1. Second Hospital of Tianjin Medical University
2. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College,
- Publication Type:Journal Article
- Keywords:
concomitant drugs;
decitabine;
JAKlS6m;
myeloproliferative neoplasms;
ruxotilinib;
TET2
- From:
Chinese Pharmacological Bulletin
2021;37(7):985-990
- CountryChina
- Language:Chinese
-
Abstract:
Aim To explore the cytotoxic and synergistic effects of decitabine and ruxolitinib on HEL cells with TET2 knockdown. Methods Stable TET2 knockdown by shRNA was established in HEL cell line. The change of cell proliferation was measured by CCK-8 assay. The median lethal dose (IC50) and colony formation assay were used to evaluate the cytotoxic effects of decitabine and ruxolitinib, the synergistic effects of which was further analyzed by Chou-Talalay method. Results The inhibition of TET2 increased the proliferative capacity of HEL cells. HEL cell lines became resistant to decitabine following shRNA-media- ted TET2 inactivation. Colony formation assay showed that the drug sensitivity of decitabine and ruxolitinib both decreased in TET2 knockdown HEL cells. The synergistic inhibitory effects of ruxolitinib and decitabine on TET2 knockdown HEL cells were observed. Conclusion The combination of ruxolitinib and decitabine may be an effective therapeutic strategy for accelerated or blast phase MPN patients with JAK2V6m and TET2 mutations.
