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NOTCH1 combined with chemotherapy synergistically inhibits triple-negative breast cancer
Wen-Jia Chen1, Hua-Tao Wu2, Yang-Zheng Lan1
1The Breast Center, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China.
Background:
Chemotherapy for triple-negative breast cancer (TNBC) is often limited in efficacy due to drug resistance. The NOTCH1 pathway significantly contributes to the advancement of tumors, but its mechanism of action in sensitizing TNBC to chemotherapy and its association with the downstream molecule, NT5E, is unclear.
Aim:
To explore the molecular mechanisms by which NOTCH1 regulates cisplatin sensitivity in TNBC cells, and to validate its synergistic effect with NT5E.
Methods:
Expression of NOTCH1 in MDA-MB-231 cells was silenced using RNA interference, and the changes in cell proliferation, migration and cisplatin sensitivity were measured in combination with cell function experiments. The regulatory relationship between NOTCH1 and NT5E was analyzed using qPCR and Western blotting, and the silencing effect of NOTCH1 was verified using NT5E overexpression experiments.
Results:
Knockdown of NOTCH1 hindered the growth and motility of TNBC cells and lowered cisplatin's half-maximal inhibitory concentration. Expression of NOTCH1 and NT5E was positively correlated, and NOTCH1 silencing led to a decrease in the expression of NT5E. Elevated NT5E expression attenuated the suppressive effects of NOTCH1 knockdown on both cell proliferation and cisplatin response.
Conclusion:
NOTCH1 enhances TNBC cisplatin chemosensitivity by regulating NT5E expression. This study provides a new target and experimental basis for the development of combination therapy strategies for TNBC.
Insights
NOTCH1 pathway activation enhances chemotherapy sensitivity in triple-negative breast cancer (TNBC) by regulating NT5E expression, offering a new therapeutic target for TNBC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) exhibits limited chemotherapy efficacy due to drug resistance.
- The NOTCH1 pathway's role in TNBC chemoresistance and its link to NT5E remain unclear.
Purpose of the Study:
- Investigate NOTCH1's molecular mechanisms in regulating cisplatin sensitivity in TNBC.
- Validate the synergistic effect of NOTCH1 and NT5E in TNBC.
Main Methods:
- Utilized RNA interference to silence NOTCH1 expression in MDA-MB-231 cells.
- Assessed changes in cell proliferation, migration, and cisplatin sensitivity.
- Analyzed NOTCH1-NT5E regulatory relationship using qPCR and Western blotting.
Main Results:
- NOTCH1 knockdown reduced TNBC cell growth, motility, and cisplatin resistance.
- NOTCH1 and NT5E expression showed a positive correlation; NOTCH1 silencing decreased NT5E levels.
- Increased NT5E expression counteracted the effects of NOTCH1 knockdown on cell proliferation and cisplatin response.
Conclusions:
- NOTCH1 enhances cisplatin chemosensitivity in TNBC by regulating NT5E expression.
- Identified NOTCH1 as a potential therapeutic target for TNBC combination therapies.
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