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Enhancement of Gene Therapy with MR-Guided Pulsed High-Intensity Focused Ultrasound (MRgHIFU) for Prostate Cancer

L Chen*, X Chen, D Cvetkovic, C Ma, Fox Chase Cancer Center, Philadelphia, PA

Presentations

(Sunday, 7/12/2020)   [Eastern Time (GMT-4)]

Room: AAPM ePoster Library

Purpose: Previous AS-MDM2 studies showed statistically insignificant AS-MDM2 uptake and tumor growth delay among groups treated with and without MRgHIFU. The aim of this investigation is to study the uptake AS-bcl-2 in prostate cancers with MRgHIFU.

Methods: Human prostate cancer LNCaP cells were implanted orthotopically in the prostate of nude mice. Tumor bearing mice were divided randomly into 4 Groups (n=5 per group): Group 1: control; Group 2: AS-bcl-2 injection (25mg/kg by tail vein) alone, with tumors removed at 4, 24, 48 and 72 hr after a single treatment respectively; Group 3: AS-bcl-2 injection once a day for 3 consecutive days; and Group 4: HIFU + AS+bcl-2 with tumor removed at 24 h after a single treatment. The tumors in Group 4 were treated using MRgHIFU under general anesthesia with an acoustic power of 4W, pulse width of 0.1 sec and 300 pulses for per sonication. Multiple sonications were used to cover the whole tumor volume. The tumors were removed and one part was snap frozen for Western blot analysis and the other part was fixed in formalin and paraffin-embedded for immunohistochemical (IHC) analysis.

Results: Our results showed that Bcl-2 expression was low in all groups (ranging from 0.4% to 0.9% on average) and there were no significant differences among the treatment groups and time points. The Bcl-2 protein expression was similar among different groups and time points based on Western blot analyses. The results from this study are in agreement with previous studies on AS-MDM2.

Conclusion: No down-regulation of Bcl-2 was observed in prostate tumors with AS-Bcl-2 or AS-Bcl-2+HIFU treatments, which may be due to a low level of expression of Bcl-2 in these tumors.
Future studies are warranted using agents that are proven to be effective in prostate cancer therapy.

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