在已開發西方國家男性中，攝護腺癌(prostate cancer, PCa)是惡性腫瘤中最嚴重的癌症之ㄧ，而其罹病率在台灣呈現逐年上升的趨勢。雖然大多數的病患可以藉由外科手術以及放射療法(ionizing radiation, IR)治癒，但在美國，每年仍有30,000人死於攝護腺癌。放射療法目前被用來治療許多種不同種類的癌症，其中包含了前期的攝護腺癌。DAB2IP(DOC-2/DAB2 interactive protein)是一種攝護腺所製造的蛋白，它可以藉由誘導細胞凋亡而抑制攝護腺癌細胞生長。藉由剔除攝護腺癌 DAB2IP 的表現，發現攝護腺癌產生了放射線抗性(radio-resistant)，因而降低了放射療法所誘導的細胞凋亡。在本篇的研究中，我們發現，由空腸彎曲桿菌(Campylobacter jejuni)中所純化出的一種細菌基因毒素(genotoxin)–細胞致死腫脹毒素(cytolethal distending toxin, CDT)可以增加攝護腺癌對於放射療法的敏感性，結合細胞致死腫脹毒素以及放射療法，我們發現可以誘導攝護腺癌細胞走向 ATM-dependent DNA 損傷反應。而在動物實驗的部分，我們也發現，細胞致死腫脹毒素可以加強放射療法對於腫瘤延遲生長的功能。這些研究結果指出合併細胞致死腫脹毒素與放射療法可以治療抗放射的攝護腺癌，特別是 DAB2IP 缺陷的表現型。
Prostate cancer (PCa) is one of the most malignancies in male in western developed countries and its incidence is rising in Taiwan. Although most patients can be cured by surgery and radiotherapy, more than 30,000 patients were died of the disease in the United States annually. Ionizing radiation (IR) is employed frequently in the management of several tumor types, including advanced PCa. DAB2IP (DOC-2/DAB2 interactive protein) is a potent growth inhibitor for PCa by inducing apoptotic pathway. By knocking down endogenous DAB2IP levels, PCa cells become resistance to IR-induced apoptosis. Our results showed that cytolethal distending toxin (CDT), a genotoxin which produced by Campylobacter jejuni, converted radio-resistance to susceptible phenotype. Combined treatment of CDT and IR induced cell death through ATM-dependent DNA damage checkpoint responses in radio-resistant PCa. Moreover, CDT significantly enhanced IR-induced tumor growth delay was observed in an animal experimental model. These findings indicate that CDT can be administered with IR to overcome radio-resistant PCa, particularly in DAB2IP-deficient phenotype.
