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Published on: June 17, 2022
[Molecular mechanism of Doxorubicin resistance in multiple myeloma cell line]
Yan-Yan Lu1, Cui-Rong Xiao1, Hua-Ying Chen1
1Department of Hematology, Xiamen University Zhongshan Hospital, Xiamen 361004,Fujian Province, China.
Abstract:
This study was aimed to investigate the molecular mechanism of doxorubicin resistance in multiple myeloma cell line and certify the effect of Notch signal over-expression on drug resistance of myeloma cells. The doxorubicin RPMI 8226 cell line (RPMI8226/DOX) was established by culturing 8226 cells with continuous low concentration and intermittent gradually-increasing-concentration of doxorubicin in vitro, the mRNA expression of Notch2,Jagged1, Jagged2, HES1 were measured by RT-PCR and the P-170 protein expression was detected by Western blot in RPMI 8226 cell line; the changes of IL-6 and VEGF were tested by ELISA. The results showed that the Notch mRNA expression (Notch2, Jagged1, Jagged2 increased gradually along with the increase of chemotherapeutic drug resistance, but the expression of HESI mRNA gradually decreased along with the increase of drug resistance. The expression level of P-170 protein was upregulated gradually along with the increase of drug resistance. The level of VEGF and IL-6 in culture supernatants of RPMI8226/DOX was higher than that in RPMI 8226. It is concluded that the establishment of RPMI 8226/DOX cell line is a useful model to analyze the mechanism of chemotherapeutic drug resistance in multiple myeloma, Notch activation is closely correlated with the drug resistance of multiple myeloma and Notch signaling may to be used as a new target for multiple myeloma treatment.
Insights
This study reveals Notch signaling activation correlates with doxorubicin resistance in multiple myeloma cells. Targeting Notch signaling may offer a new therapeutic strategy for overcoming drug resistance in myeloma.
Area of Science:
- Molecular Biology
- Cell Biology
- Pharmacology
Context:
- Multiple myeloma is a hematological malignancy characterized by uncontrolled proliferation of plasma cells.
- Acquired resistance to chemotherapeutic agents like doxorubicin poses a significant challenge in multiple myeloma treatment.
- Understanding the molecular mechanisms underlying drug resistance is crucial for developing effective therapeutic strategies.
Purpose:
- To investigate the molecular mechanisms of doxorubicin resistance in a multiple myeloma cell line.
- To evaluate the impact of Notch signaling pathway activation on drug resistance in multiple myeloma.
- To establish a doxorubicin-resistant multiple myeloma cell line for further mechanistic studies.
Summary:
- A doxorubicin-resistant RPMI 8226 cell line (RPMI8226/DOX) was established and characterized.
- Increased mRNA expression of Notch2, Jagged1, and Jagged2, along with elevated P-170 protein and higher levels of VEGF and IL-6, were observed in resistant cells.
- Conversely, HES1 mRNA expression decreased with increasing drug resistance.
Impact:
- The RPMI8226/DOX cell line serves as a valuable model for studying chemotherapeutic drug resistance in multiple myeloma.
- Notch pathway activation is identified as a key factor associated with drug resistance in multiple myeloma.
- The findings suggest that Notch signaling could be a potential therapeutic target for overcoming doxorubicin resistance in multiple myeloma.
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