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Targeting glutaminase1 and synergizing with clinical drugs achieved more promising antitumor activity on multiple myeloma.

ABSTRACT: Multiple myeloma (MM) pathogenesis remains incompletely understood and biomarkers predicting treatment response still remain lacking. Here we describe the rational mechanisms of combining targeting glautaminase1 (GLS1) with other chemo-reagents for MM treatment. Gls1 is highly expressed cMYC/KRAS12V-drived plasmacytoma (PCT) cells. Down-regulation of Gls1 with miRNAi in cMYC/KRAS12V-expressing BaF3 cells prevented them from growing independence of interleukin 3 (IL3). By using our cMYC/KRAS12V-transduced adoptive plasmacytoma mouse model, we found that Gls1 is involved in PCT pathogenesis. Down-regulation of Gls1 significantly prolonged the survival of PCT recipients. Knockdown of Gls1 increased the expression of Cdkn1a and Cdkn1b and decreased the expression of some critical oncogenes for cancer cell survival, such as c-Myc, Cdk4, and Nf?B, as well as some genes which are essential for MM cell survival, such as Irf4, Prdm1, Csnk1?1, and Rassf5. Combination of Gls1 inhibition with LBH589, Bortezomib, or Lenalidomide significantly impaired tumor growth in a MM xenograft mouse model. Our data strongly suggest that Gls1 plays an important role for MM pathogenesis and that combination of GLS1 inhibitor with other MM therapy agents could benefit to MM patients.

SUBMITTER: Qiu Q

PROVIDER: S-EPMC6800263 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Targeting glutaminase1 and synergizing with clinical drugs achieved more promising antitumor activity on multiple myeloma.

Qiu Qiang Q Li Mengyuan M Yang Linyu L Tang Minghai M Zheng Li L Wang Fang F Qiu Huandi H Liang Cailing C Li Ning N Yi Dongni D Yi Yuyao Y Pan Cong C Yang Shengyong S Chen Lijuan L Hu Yiguo Y

Oncotarget 20191015 57

Multiple myeloma (MM) pathogenesis remains incompletely understood and biomarkers predicting treatment response still remain lacking. Here we describe the rational mechanisms of combining targeting glautaminase1 (GLS1) with other chemo-reagents for MM treatment. Gls1 is highly expressed cMYC/KRAS12V-drived plasmacytoma (PCT) cells. Down-regulation of Gls1 with miRNAi in cMYC/KRAS12V-expressing BaF3 cells prevented them from growing independence of interleukin 3 (IL3). By using our cMYC/KRAS12V-t ...[more]

PMID: 31666930

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Dataset Information

Targeting glutaminase1 and synergizing with clinical drugs achieved more promising antitumor activity on multiple myeloma.

Publications

Targeting glutaminase1 and synergizing with clinical drugs achieved more promising antitumor activity on multiple myeloma.

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