Autophagy and enhanced chemosensitivity in experimental pancreatic cancers induced by noninvasive radiofrequency field treatment.

Abstract

BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDAC) have limited therapeutic options and poor response to the standard gemcitabine (GCB)-based chemotherapy. In the current study, the authors investigated the feasibility of noninvasive short-wave radiofrequency (RF) electric fields to improve the cytotoxic effect of GCB on PDAC cells and determined its mechanism of action. METHODS: The cytotoxicity of RF alone and in combination with GCB was studied in vitro on normal pancreatic human pancreatic ductal epithelial cells and different PDAC cell lines by flow cytometry, and in vivo on ectopic and orthotopic human PDAC xenograft models in mice. The mechanism of RF activity was studied by Western blot analysis and immunohistochemistry. Toxicity was determined by histopathology. RESULTS: Exposure of different PDAC cells to 13.56-megahertz radio waves resulted in a substantial cytotoxic effect, which was accompanied by the induction of autophagy but not apoptosis. These effects of RF were found to be absent in normal cells. Excessive numbers of autophagosomes in cancer cells persisted 24 to 48 hours after RF exposure and then declined. The addition of a subtoxic dose of GCB to RF treatment inhibited the recovery of cancer cells from the RF-induced autophagy and enhanced the cytotoxic effect of the latter on cancer cells. The treatment of PDAC in situ in mice with the combination of noninvasive RF and GCB was found to have a superior antitumor effect compared with the use of RF or GCB alone, yet there was no evidence of systemic toxicity. CONCLUSIONS: Noninvasive RF treatment induced autophagy but not apoptosis in cancer cells and demonstrated potential as an enhancer of chemotherapy for treating patients with pancreatic cancer without toxicity to normal cells.

AI evidence extraction

Main findings

Exposure of PDAC cells to 13.56 MHz radio waves produced substantial cytotoxicity accompanied by induction of autophagy but not apoptosis; these effects were reported as absent in normal pancreatic ductal epithelial cells. Combining RF with a subtoxic dose of gemcitabine inhibited recovery from RF-induced autophagy and enhanced cytotoxicity in vitro, and showed superior antitumor effects versus RF or gemcitabine alone in mouse PDAC xenografts without evidence of systemic toxicity.

Outcomes measured

• Cytotoxicity/cell death
• Autophagy induction
• Apoptosis markers
• Tumor response/antitumor effect in xenograft models
• Systemic toxicity (histopathology)

Limitations

• Sample size not reported in abstract
• Exposure metrics beyond frequency (e.g., field strength, SAR, duration) not provided in abstract
• Preclinical design (cell lines and mouse xenografts) limits direct inference to clinical outcomes

Suggested hubs

• rf-cancer-therapy (0.9)
  Study evaluates noninvasive RF electric fields as an antitumor/chemosensitizing treatment in pancreatic cancer models.

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        "source": "other",
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        "sar_wkg": null,
        "duration": null
    },
    "population": "Human pancreatic ductal epithelial cells and pancreatic ductal adenocarcinoma (PDAC) cell lines (in vitro); human PDAC xenograft models in mice (in vivo)",
    "sample_size": null,
    "outcomes": [
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        "Systemic toxicity (histopathology)"
    ],
    "main_findings": "Exposure of PDAC cells to 13.56 MHz radio waves produced substantial cytotoxicity accompanied by induction of autophagy but not apoptosis; these effects were reported as absent in normal pancreatic ductal epithelial cells. Combining RF with a subtoxic dose of gemcitabine inhibited recovery from RF-induced autophagy and enhanced cytotoxicity in vitro, and showed superior antitumor effects versus RF or gemcitabine alone in mouse PDAC xenografts without evidence of systemic toxicity.",
    "effect_direction": "benefit",
    "limitations": [
        "Sample size not reported in abstract",
        "Exposure metrics beyond frequency (e.g., field strength, SAR, duration) not provided in abstract",
        "Preclinical design (cell lines and mouse xenografts) limits direct inference to clinical outcomes"
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "radiofrequency",
        "13.56 MHz",
        "short-wave",
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        "pancreatic ductal adenocarcinoma",
        "gemcitabine",
        "chemosensitization",
        "autophagy",
        "xenograft",
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    ],
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