Research Paper Volume 13, Issue 5 pp 6820—6831
Nicardipine sensitizes temozolomide by inhibiting autophagy and promoting cell apoptosis in glioma stem cells
- 1 Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou, China
- 2 Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Changzhou, China
Received: July 15, 2020 Accepted: December 18, 2020 Published: February 17, 2021https://doi.org/10.18632/aging.202539
How to Cite
Copyright: © 2021 Shi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Glioblastoma multiforme (GBM) is the most invasive malignant central nervous system tumor with poor prognosis. Nicardipine, a dihydropyridine calcium channel antagonist, has been used as an adjuvant to enhance sensitivity to chemotherapeutic drugs. However, whether glioma stem cells (GSCs) can be sensitized to chemotherapy via combined treatment with temozolomide (TMZ) and nicardipine is unclear. In this study, surgical specimen derived GSCs SU4 and SU5 were applied to explore the sensitization effect of nicardipine on temozolomide against GSCs, and further explore the relevant molecular mechanisms. Our results showed that nicardipine can enhance the toxic effect of temozolomide against GSCs, promote apoptosis of GSCs, and inhibit autophagy of GSCs. The relevant mechanisms were related to activation of mTOR, and selective inhibition of mTOR by rapamycin could weaken the sensitization of nicardipine to temozolomide, which suggest that nicardipine can be applied as an adjuvant to inhibit autophagy in GSCs, and enhance apoptosis-promoting effect of temozolomide in GSCs as well. Nicardipine can inhibit autophagy by activating expression of mTOR, thus play tumor inhibition roles both in vitro and in vivo. Repurposing of nicardipine can help to improving therapeutic effect of TMZ against GBM, which deserves further clinical investigations.
Nic: Nicardipine; GSCs: glioma stem cells; TMZ: Temozolomide; GBM: Glioblastoma multiforme Methylguanine; MGMT: methyltransferase; CQ: Chloroquine; FITC: Fluorescein isothiocyanate; PI: Propidium iodide.