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Published on: May 15, 2019
[Mechanism concerning antitumor effect of oridonin on multiple myeloma cell line U266]
Hao-Qing Duan1, Mian-Yang Li2, Li Gao3
1College of Laboratorial Medicine and College of Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China; Department of Clinical Laboratorial Examination, Chinese PLA General Hospital, Bejing 100853, China.
Abstract:
This study was purposed to investigate the antitumor effect of oridonin on human multiple myeloma cell line U266 and its possible mechanism. The CCK-8 test was used to determine the inhibitory effect of oridonin on proliferation of U266 cells. The morphological changes of U266 cells were observed under optical microscope. The apoptosis rate of U266 cells was detected by flow cytometry. The mRNA levels of FGFR3, BCL2, CCND1 and MYC genes were quantified by using real-time quantitative PCR method, and the protein levels of BCL2, MYC, CCND1, FGFR3 and P53 were detected by Western blot. The results showed that the oridonin obviously inhibited the growth of U266 cell in dose-and time-dependent manners. As for morphological changes, characteristic apoptotic cells presented in U266 cells treated with 10 µmol/L oridonin for 24 hours. The apoptotic rate of U266 cells increased in dose and time dependent manners; after treatment of U266 cells with oridonin the mRNA levels of FGFR3, BCL2, CCND1 and MYC as well as the their protein levels decreased. Occasionally, the oridonin up-regulated the protein levels of P53 in the same manner. It is concluded that the oridonin can exert its anti-tumor effect by inhibiting proliferation and inducing apoptosis of U266 cell in dose dependent and time dependent manners, that maybe give the clues about new program of target therapy for multiple myeloma.
Insights
Oridonin effectively inhibits human multiple myeloma U266 cell growth and induces apoptosis. This compound downregulates key genes like FGFR3, BCL2, CCND1, and MYC, offering potential for targeted multiple myeloma therapies.
Area of Science:
- Pharmacology
- Molecular Biology
- Oncology
Context:
- Multiple myeloma is a hematological malignancy with limited treatment options.
- Understanding novel therapeutic agents is crucial for improving patient outcomes.
Purpose:
- To investigate the antitumor effects of oridonin on the human multiple myeloma cell line U266.
- To elucidate the underlying molecular mechanisms of oridonin's action.
Summary:
- Oridonin demonstrated significant inhibition of U266 cell proliferation in a dose- and time-dependent manner.
- Morphological analysis revealed oridonin-induced apoptosis, confirmed by flow cytometry.
- Oridonin treatment led to decreased mRNA and protein levels of FGFR3, BCL2, CCND1, and MYC, with a notable upregulation of P53 protein.
Impact:
- Oridonin exhibits potent anti-multiple myeloma activity by inhibiting cell proliferation and inducing apoptosis.
- The findings suggest oridonin as a potential candidate for targeted therapy in multiple myeloma treatment regimens.
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