Studies on the relation between drug sensitivity and transporters in cancer for tailor-made cancer chemotherapy

在这项研究中，我们揭示了“体内耐药”在肝细胞癌和肾细胞癌。癌细胞仅在宿主体内增殖时对顺铂耐药，但体外培养后，药物敏感性显著增加。我们阐明了体内耐药的机制。细胞膜上表达多种ABC转运蛋白，在体外培养过程中转运蛋白间的MRP 2表达消失，加入结合胆红素后表达增加。这些结果有力地表明，当癌细胞在宿主中生长时，胆红素诱导的MRP 2挤出包括顺铂在内的抗癌药物，并且癌细胞对抗癌药物具有抗性。另一方面，MRP2的表达水平在来自患者的癌标本中有很大差异。因此，检测肿瘤活检组织中转运蛋白的表达水平，对肿瘤的化疗有重要的指导意义。

In this study, we revealed the "in vivo drug resistance" in hepatocellular carcinomas and renal cell carcinoma. The cancer cells are resistant to cicplatin only in proliferating in the host, but when they were incubated in vitro, the drug sensitivity is markedly increased. We clarified the mechanisms of the in vivo drug resistance. The cells express several ABC transporters on the plasma membrane, and the expression of MRP2 among transporters was disappeared during in vitro culture and was incresed by addition of conjugated bilirubin. These results strongly suggest when cancer cells are growing in the host, MRP2 induced by bilirubin extrude anticancer drugs including cisplatin and the cancer cells are resistant to the anticancer drugs. On the other hand, the expression level of MRP2 was quite different among cancer specimens from patients. Therefore, estimation of the transporter expression level of cancer biopsy specimens may be very useful for cancer chemotherapy and become the tailor-made chemotherapy.