Microbubble-Mediated Cavitation Promotes Apoptosis and Suppresses Invasion in AsPC-1 Cells
Jing Cao1, Chenlu Hu2, Hang Zhou1
1Department of Ultrasound, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Abstract:
The aim of this study was to identify the potential and mechanisms of microbubble-mediated cavitation in promoting apoptosis and suppressing invasion in cancer cells. AsPC-1 cells were used and divided into four groups: control group, microbubble-only (MB) group, ultrasound-only (US) group and ultrasound plus microbubble (US + MB) group. Pulse ultrasound was used at a frequency of 360 kHz and a SPPA (spatial peak, pulse average) intensity of 1.4 W/cm2 for 1 min (duty rate = 50%). Then cells in the four groups were cultured for 24 h. Cell Counting Kit‑8 (Biosharp, Hefei, Anhui, China) revealed decreased cell viability in the US + MB group. Western blot confirmed that there were increased cleaved caspase‑3 and Bcl-2-associated X protein levels and decreased B‑cell lymphoma‑2 (Bcl-2) levels, as well as increased intracellular calcium ions and downregulated cleaved caspase-8, in the US + MB group. With respect to proliferation, cells in the US + MB group had lower expression of Ki67 and the weakened colony formation ability. The transwell invasion assay revealed that invasion ability could be decreased in AsPC-1 cells in the US + MB group. Further, it was found that cells in the US + MB group had lower levels of hypoxia-inducible factor-1α (HIF-1α) and vimentin and higher levels of E-cadherin compared with the other three groups. Finally, the US + MB cells had less invadopodium formation. In conclusion, these results suggest that microbubble-mediated cavitation promotes apoptosis and suppresses invasion in AsPC-1 cells.
Insights
Microbubble-mediated cavitation effectively promotes cancer cell apoptosis and suppresses invasion. This ultrasound and microbubble combination therapy shows potential for cancer treatment by inducing cell death and reducing metastasis.
Area of Science:
- Oncology
- Biophysics
- Cell Biology
Background:
- Cancer cell invasion and apoptosis resistance are critical challenges in oncology.
- Microbubble-mediated cavitation is an emerging therapeutic modality with potential anti-cancer effects.
Purpose of the Study:
- To investigate the mechanisms by which microbubble-mediated cavitation influences apoptosis and invasion in AsPC-1 cancer cells.
- To evaluate the efficacy of combined ultrasound and microbubble treatment on cancer cell behavior.
Main Methods:
- AsPC-1 cells were treated with ultrasound (US) and microbubbles (MB), alone or in combination (US + MB).
- Cell viability was assessed using Cell Counting Kit-8.
- Apoptosis markers (caspase-3, Bcl-2, Bcl-2-associated X protein), proliferation marker (Ki67), invasion markers (HIF-1α, vimentin, E-cadherin), and invadopodium formation were analyzed.
- Intracellular calcium ion levels were measured.
Main Results:
- Combined US + MB treatment significantly decreased AsPC-1 cell viability and proliferation (lower Ki67, weakened colony formation).
- US + MB induced apoptosis, evidenced by increased cleaved caspase-3 and Bcl-2-associated X protein, and decreased Bcl-2 levels.
- Invasion was suppressed, with reduced intracellular calcium ions, lower HIF-1α and vimentin, higher E-cadherin, and less invadopodium formation.
Conclusions:
- Microbubble-mediated cavitation effectively promotes apoptosis in AsPC-1 cells.
- This approach significantly suppresses cancer cell invasion and metastasis-associated markers.
- Combined ultrasound and microbubble therapy presents a promising strategy for cancer treatment by targeting both cell death and invasion pathways.
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