Synergistic combination of topotecan and low-intensity ultrasound to enhance HepG2 cell apoptosis

Abstract

Abstract: AIM: To study the combined effects of low-intensity pulsed ultrasound (LIPUS) and topotecan (TOP) on cell apoptosis induction of HepG2 cells and the mechanisms involved. METHODS: Human liver cancer HepG2 cells were used for the experiments. Experiments were conducted in 4 groups: non-treated, TOP treated, ultrasound treated, and combined (TOP+LIPUS). The viability was evaluated by trypan blue dye exclusion test and apoptosis and incorporation of TOP was assessed by flow cytometry. Involvement of sonoporation in molecular incorporation was evaluated using FITC-dextran. RESULTS: Synergistic enhancement in cell killing and additive enhancement in induction of apoptosis were observed at and above 0.8W/cm². Incorporation of TOP was increased 12.88% in combined group (vs. TOP) at 1.0W/cm². Increasing in incorporation of the TOP by cavitation and ultrasound were the mechanisms of enhancements. CONCLUSION: Combination of TOP and LIPUS can enhance the effect of apoptosis induction, and cavitation is the main mechanism for their synergistic.

Key words: HepG2, Low-intensity ultrasound, Topotecan, Apoptosis

CLC Number:

R965.2

QIU Ri-xiang, WANG Yan-li, CHEN Yang-di, LIN YAN, YANG Feng, CHEN Zhi-yi. Synergistic combination of topotecan and low-intensity ultrasound to enhance HepG2 cell apoptosis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(12): 1384-1388.

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