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Updated: Jul 16, 2026
Repression of Multiple Myeloma Cell Growth In Vivo by Single-wall Carbon Nanotube (SWCNT)-delivered MALAT1 Antisense Oligos
Published on: December 13, 2018
Experimental study enhancing the chemosensitivity of multiple myeloma to melphalan by using a tissue-specific
Zhen-Zhou Yang1, Xing-Hua Chen, Dong Wang
1Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, PR China.
Purpose:
Because of a developing resistance to chemotherapy agents, multiple myeloma (MM) has been an incurable disease until now. As a means to overcome MM tumor cell resistance and/or sensitize tumor cells to chemotherapeutic treatments currently used, we examined the role of human apurinic/apyrimidinic endonuclease 1 (APE1) in resistance and prognosis in patients with MM.
Patients And Methods:
Multiple myeloma cells were analyzed by using bone marrow specimens from 32 patients with MM and 10 normal volunteers.
Results:
The positive rate of APE1 protein expression was 65.6% in the bone marrow specimens of patients with MM with known clinical outcome. Positive rate of APE1 expression beyond grade 2 in the relapsed/refractory group was significantly higher than that in the untreated group. No positive results of grade > 2 were detected in bone marrow specimens from patients with noncancerous disease. It was also confirmed that the amount of APE1 protein in KM3 cells was positively correlated with the dose and action time of melphalan. Because APE1 was overexpressed in refractory/relapsed MM cells, siRNA-targeted technology was used to decrease APE1 levels in KM3 cells, with protein levels deceasing to 80%-90% within 24 hours and continuing to decease for 72 hours. The best dose and time of inhibiting expression of APE1 protein were 3 mug and 2 days long. A decrease in APE1 levels in siRNA-treated KM3 cells led to enhanced cell sensitization to melphalan.
Conclusion:
The findings herein present prognostic and therapeutic implications for treating relapsed/refractory MM. The APE1-silencing RNA results demonstrate the feasibility of the therapeutic modulation of APE1 using a variety of molecules and approaches.
Insights
Human apurinic/apyrimidinic endonuclease 1 (APE1) is overexpressed in multiple myeloma, contributing to chemotherapy resistance. Inhibiting APE1 enhances sensitivity to melphalan, offering new therapeutic strategies for refractory cases.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Multiple myeloma (MM) remains largely incurable due to developing resistance to chemotherapy.
- Human apurinic/apyrimidinic endonuclease 1 (APE1) plays a role in DNA repair and may influence cancer cell resistance.
- Understanding APE1's role is crucial for developing novel therapeutic strategies against MM.
Purpose of the Study:
- To investigate the role of APE1 in chemotherapy resistance and prognosis in multiple myeloma patients.
- To determine if APE1 expression levels correlate with disease status (untreated vs. relapsed/refractory).
- To assess the therapeutic potential of targeting APE1 to overcome melphalan resistance in MM cells.
Main Methods:
- Analysis of bone marrow specimens from 32 MM patients and 10 healthy volunteers.
- Assessment of APE1 protein expression levels using immunohistochemistry.
- Correlation analysis between APE1 expression and clinical outcome.
- In vitro studies using KM3 MM cells treated with melphalan and siRNA targeting APE1.
Main Results:
- APE1 protein expression was detected in 65.6% of MM patient samples.
- Higher APE1 expression (grade > 2) was significantly associated with relapsed/refractory MM compared to untreated MM.
- APE1 protein levels in KM3 cells positively correlated with melphalan dose and treatment duration.
- siRNA-mediated APE1 knockdown in KM3 cells enhanced sensitivity to melphalan.
Conclusions:
- APE1 overexpression is linked to poor prognosis and refractoriness in multiple myeloma.
- Targeting APE1 with siRNA demonstrates a feasible therapeutic approach to sensitize MM cells to chemotherapy.
- These findings suggest APE1 as a potential prognostic marker and therapeutic target for relapsed/refractory MM.
