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Unite and Conquer: Association of Two G-Quadruplex Aptamers Provides Antiproliferative and Antimigration Activity for
Svetlana Pavlova1,2, Lika Fab1, Fatima Dzarieva1,2
1Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia.
Abstract:
Background: High-grade gliomas remain a virtually incurable form of brain cancer. Current therapies are unable to completely eradicate the tumor, and the tumor cells that survive chemotherapy or radiation therapy often become more aggressive and resistant to further treatment, leading to inevitable relapses. While the antiproliferative effects of new therapeutic molecules are typically the primary focus of research, less attention is given to their influence on tumor cell migratory activity, which can play a significant role in recurrence. A potential solution may lie in the synergistic effects of multiple drugs on the tumor. Objectives: In this study, we investigated the effect of combined exposure to bi-(AID-1-T), an anti-proliferative aptamer, and its analog bi-(AID-1-C), on the migratory activity of human GBM cells. Results: We examined the effects of various sequences of adding bi-(AID-1-T) and bi-(AID-1-C) on five human GBM cell cultures. Our findings indicate that certain sequences significantly reduced the ability of tumor cells to migrate and proliferate. Additionally, the expression of Nestin, PARP1, L1CAM, Caveolin-1, and c-Myc was downregulated in human GBM cells that survived exposure, suggesting that the treatment had a persistent antitumor effect on these cells.
Insights
Combined aptamers bi-(AID-1-T) and bi-(AID-1-C) significantly reduced glioblastoma cell migration and proliferation. Surviving cells showed persistent antitumor effects, impacting key protein expression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- High-grade gliomas (GBM) are aggressive brain cancers with poor prognoses.
- Current treatments often lead to resistant, recurrent tumors.
- Tumor cell migration is a critical factor in cancer recurrence, yet often overlooked.
Purpose of the Study:
- To investigate the combined effects of aptamers bi-(AID-1-T) and bi-(AID-1-C) on human GBM cell migration.
- To explore potential synergistic therapeutic strategies for glioblastoma.
Main Methods:
- Exposure of five human GBM cell cultures to different sequences of bi-(AID-1-T) and bi-(AID-1-C).
- Assessment of tumor cell migratory and proliferative activities.
- Analysis of protein expression (Nestin, PARP1, L1CAM, Caveolin-1, c-Myc) in surviving cells.
Main Results:
- Specific sequences of combined aptamer treatment significantly inhibited GBM cell migration and proliferation.
- Downregulation of Nestin, PARP1, L1CAM, Caveolin-1, and c-Myc was observed in surviving GBM cells.
- Evidence of a persistent antitumor effect following combined aptamer exposure.
Conclusions:
- Combined aptamer therapy shows promise in reducing GBM cell migration and proliferation.
- The observed downregulation of key proteins suggests a lasting impact on tumor cell behavior.
- This approach may offer a novel strategy to combat glioblastoma recurrence.
