BMC Cancer, 2007, 7(1):4.

Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

Gilda G Hillman, Yu Wang, Mingxin Che, et al

Department of Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA; et al

BACKGROUND:

We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC) model established in our laboratory.

METHODS:

The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs.

RESULTS:

In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer.

CONCLUSION:

Our studies in both RCC and prostate tumor models demonstrate that the combination of genistein with primary tumor irradiation is a more effective and safer therapeutic approach as the tumor growth and progression are inhibited both in the primary and metastatic sites.

英国《BMC癌症》，2007年

在原位模型中，金雀异黄素和放射线抑制肾细胞癌的进展

吉尔达 G 希尔曼，王宇，车明鑫，等

放射肿瘤学，芭芭拉·安Karmanos癌症研究所，医学院，密歇根州底特律的韦恩州立大学学系，美国；等

背景：

我们以前报道过使用前列腺肿瘤细胞的大豆异黄酮染料木素对前列腺癌的放射治疗的增强作用体外和原位前列腺肿瘤模型在体内。然而，当染料木素用作动物模型中的单一疗法时，它被促进转移到区域性主动脉旁淋巴结。阐明染料木素的这些有趣的副作用是否是原位固有的前列腺肿瘤模型，或这些结果也可以在另一个模型中重述，我们使用原位转移性KCI-18肾细胞我们实验室建立的癌（RCC）模型。

方法：

从具有乳头状肾细胞癌的患者产生KCI-18RCC细胞系。 KCI-18的原位肾移植术后RCC细胞和裸鼠系列体内肾传代，我们建立了可靠和可预测的转移性RCC肿瘤模型。老鼠用染料木素联合肾肿瘤照射处理建立的肾肿瘤。评估治疗的效果对原发肿瘤和转移到各种器官。

结果：

在该实验模型中，保留了人原发肿瘤的核型和组织学特征。肿瘤细胞转移从原发性肾肿瘤到肺部，肝和肠系膜模拟人类RCC的进展。治疗已建立的肾脏染料木素的肿瘤表现出刺激原发性肾脏肿瘤生长并增加转移发生率的趋势到排便肠的肠系膜。相反，当与肾肿瘤照射相结合时，染料木素显着抑制已建立的肾肿瘤的生长和进展。这些发现证实了染料木素放射治疗在原位增强RCC模型如之前在前列腺癌的原位模型中所示。

结论：

我们在RCC和前列腺肿瘤模型中的研究表明，染料木素与原发性肿瘤照射的结合更多有效和安全的治疗方法，因为在初级和转移部位都能抑制肿瘤生长和进展。