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Hyperthermia, which is a noninvasive treatment that causes tumor cells to become heated and that works in synergy with anticancer drugs and radiation therapy, is emerging as a promising treatment for patients with cancer. The purpose of this study is to report the efficacy of hyperthermia combined with chemotherapy (gemcitabine/cisplatin) for the treatment of a patient with unresectable cholangiocarcinoma. A 54-year-old man was diagnosed as hilar cholangiocarcinoma (Klatskin tumor) and was administered neoadjuvant and preoperative radiation with chemotherapy. However, because the treatment with radiation and chemotherapy was not successful, he decided to undergo hyperthermia combined with chemotherapy as a second treatment option. He was suffering from fatigue, dyspepsia, epigastralgia, and jaundice. Hyperthermia combined with chemotherapy was administered 32 times over a period of 4 months. The patient experienced no critical complications, and the patient’s condition improved, with the carbohydrate antigen 19-9 (CA 19-9) and the total bilirubin levels being relatively lowered. In addition, the computed tomography scan showed that the cholangiocarcinoma had not progressed. In conclusion, this case report suggests radiofrequency hyperthermia combined with chemotherapy may be a promising treatment option for patients with unresectable cholangiocarcinoma.

Houttuynia cordata Thunb ( H cordata), a medicinal plant, has anticancer activity, as it inhibits cell growth and induces cell apoptosis in cancer. However, the potential anti-cancer activity and mechanism of H cordata for human liver cancer cells is not well understood. Recently, we identified hypoxia-inducible factor (HIF)-1A, Forkhead box (FOX)O3, and MEF2A as proapoptotic factors induced by H cordata, suggesting that HIF-1A, FOXO3, and MEF2A contribute to the apoptosis of HepG2 hepatocellular carcinoma cells. FOXO3 transcription factors regulate target genes involved in apoptosis. H cordata significantly increased the mRNA and protein expression of HIF-1A and FOXO3 and stimulated MEF2A expression in addition to increased apoptosis in HepG2 cells within 24 hours. Therefore, we determined the potential role of FOXO3 on apoptosis and on H cordata–induced MEF2A in HepG2 cells. HIF-1A silencing by siRNA attenuated MEF2A and H cordata–mediated FOXO3 upregulation in HepG2 cells. Furthermore, H cordata–mediated MEF2A expression enhanced caspase-3 and caspase-7, which were abolished on silencing FOXO3 with siRNA. In addition, H cordata inhibited growth of human hepatocellular carcinoma xenografts in nude mice. Taken together, our results demonstrate that H cordata enhances HIF-1A/FOXO3 signaling, leading to MEF2A upregulation in HepG2 cells, and in parallel, it disturbs the expression of Bcl-2 family proteins (Bax, Bcl-2, and Bcl-xL), which results in apoptosis. Taken together, these findings demonstrate that H cordata promotes the activation of HIF-1A–FOXO3 and MEF2A pathways to induce apoptosis in human HepG2 hepatocellular carcinoma cells and is, therefore, a promising candidate for antitumor drug development.