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Published on: December 15, 2010
[Effect of DR5-mediated docetaxel-loaded lipid microbubble combined with ultrasoundtargeted microbubble destruction
1Department of Gastroenterology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Objective:
To investigate the effect of DR5-mediated docetaxel-targeted lipid microbubbles (MBs) combined with ultrasound-targeted microbubble destruction on apoptosis and expressions of Bcl-2, nuclear factor-κB(NF-κB), caspase-8, and DR5 in human HepG2 cells.
Methods:
HepG2 cells were treated with docetaxel at its 50% inhibitory concentration (IC50) of 5 nmol/L, docetaxel combined with ultrasound, blank MBs, blank MBs combined with ultrasound (0.5 W/cm2 for 45 s), drugloaded lipid MBs (DLLM), DLLM combined with ultrasound, DR5-mediated DLLM (DR5-DLLM), or DR5-DLLM combined with ultrasound.After the treatments, the cells were further cultured for 24 h, and CCK-8 assay, TUNEL staining and flow cytometry were used to assess cell proliferation, apoptosis, and cell cycle changes; the changes in mRNA and protein expression levels of Bcl-2, NF-κB, caspase-8, and DR5 were detected with RT-qPCR and Western blotting.
Results:
Among all the treatments, DR5-DLLM combined with ultrasound produced the strongest effects to inhibit the proliferation (P < 0.001), promote apoptosis (P < 0.001), and cause G2/M cell cycle arrest (P < 0.001) in HepG2 cells.The combined treatment with DR5-DLLM and ultrasound also significantly downregulated Bcl-2 and NF-κB (P < 0.001) and upregulated DR5 and caspase-8 expressions (P < 0.001) at both the mRNA and protein levels.
Conclusion:
DR5-DLLM combined with ultrasound-targeted microbubble destruction can induce G2/M cell cycle arrest, proliferation inhibition and apoptosis in HepG2 cells by downregulating Bcl-2 and NF-κB and upregulating DR5 and caspase-8 expressions, indicating its value as a novel ultrasoundtargeted therapy for liver cancer.
Insights
The combination of DR5-mediated docetaxel-loaded lipid microbubbles (DLLM) and ultrasound-targeted microbubble destruction effectively inhibits HepG2 cell proliferation and induces apoptosis. This novel therapy upregulates DR5 and caspase-8 while downregulating Bcl-2 and NF-κB, showing promise for liver cancer treatment.
Area of Science:
- Oncology
- Biotechnology
- Nanomedicine
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge.
- Targeted drug delivery systems offer potential for improved cancer therapy efficacy.
- Microbubbles combined with ultrasound present a novel approach for localized cancer treatment.
Purpose of the Study:
- To evaluate the synergistic effects of DR5-mediated docetaxel-loaded lipid microbubbles (DLLM) with ultrasound-targeted microbubble destruction.
- To investigate the impact of this combined therapy on HepG2 cell apoptosis and key protein expressions.
- To assess the potential of this novel approach as an ultrasound-targeted therapy for liver cancer.
Main Methods:
- HepG2 cells were treated with various combinations of docetaxel, microbubbles (MBs), and ultrasound.
- Drug-loaded lipid MBs (DLLM) and DR5-mediated DLLM (DR5-DLLM) were utilized.
- Cell proliferation, apoptosis, cell cycle, and protein/mRNA expressions (Bcl-2, NF-κB, caspase-8, DR5) were analyzed using CCK-8, TUNEL, flow cytometry, RT-qPCR, and Western blotting.
Main Results:
- DR5-DLLM combined with ultrasound demonstrated the most significant inhibition of HepG2 cell proliferation and induction of apoptosis (P < 0.001).
- This combination also caused significant G2/M cell cycle arrest (P < 0.001).
- The treatment significantly downregulated Bcl-2 and NF-κB while upregulating DR5 and caspase-8 at both mRNA and protein levels (P < 0.001).
Conclusions:
- DR5-DLLM combined with ultrasound-targeted microbubble destruction is a potent strategy for inducing apoptosis and inhibiting proliferation in HepG2 cells.
- The mechanism involves the downregulation of Bcl-2 and NF-κB, and upregulation of DR5 and caspase-8.
- This approach holds significant promise as a novel ultrasound-targeted therapy for liver cancer.
