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| Status |
Public on Jun 26, 2024 |
| Title |
Deoxypodophyllotoxin suppresses Malignant pleural mesothelioma growth via mitotic dependent necroptosis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with a poor prognosis. Patients are typically diagnosed at an advanced stage due to the disease's long incubation period. Limited therapeutic advancements in the last two decades have prompted further investigation into alternative treatments. Previous studies have identified significant dysregulation in the mitotic spindle assembly checkpoint pathway and microtubule network of MPM, underscoring the potential of targeting microtubules in managing MPM. Deoxypodophyllotoxin (DPT) is a novel microtubule-targeting drug that has demonstrated promising therapeutic efficacy in various cancers. While the precise mechanism of DPT's anti-MPM effect remains undisclosed, our research indicates that DPT inhibits MPM growth in a dose-dependent manner both in vitro and in vivo. Moreover, it exhibits a favorable safety profile and shows lower toxicity towards normal cells and mice at therapeutic doses. Mechanistic studies involving three MPM cell lines (MSTO-211H, H2452, and H28) revealed that DPT induces multinucleated and micronucleated cells, disrupts spindle formation, and triggers Mitosis cell cycle arrest and necroptosis in tumor cells. In conclusion, our findings suggest that DPT holds promise as a safe and effective therapeutic option for MPM.
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| Overall design |
Extract total RNA from MPM H2452 cells treated with DPT (20nM) or DMSO (control) 48h. We analyzed the differentially expressed genes between the treatment group and the control group using RNA. Both groups were treated in four biological replicates.
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| Contributor(s) |
Zhong C, Sun R, Ren T |
| Citation missing |
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| Submission date |
Jun 20, 2024 |
| Last update date |
Jun 26, 2024 |
| Contact name |
Cheng Zhong |
| E-mail(s) |
zhongcheng777@sjtu.edu.cn
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| Organization name |
Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University
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| Department |
Department of Respiratory Medicine
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| Street address |
Yishan road 600, Xuhui District, Shanghai, China
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| City |
Shanghai |
| State/province |
Shanghai |
| ZIP/Postal code |
200030 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| GSM8341530 |
H2452 DMSO,48h,rep 4 |
| GSM8341531 |
H2452 DPT,48h,rep 1 |
| GSM8341532 |
H2452 DPT,48h,rep 2 |
| GSM8341533 |
H2452 DPT,48h,rep 3 |
| GSM8341534 |
H2452 DPT,48h,rep 4 |
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| Relations |
| BioProject |
PRJNA1126279 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE270379_all.genes.expression.annot.txt.gz |
4.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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