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

在这项研究中，我们揭示了肝细胞癌和肾细胞癌的“体内耐药”。肿瘤细胞仅在宿主体内增殖时对顺铂具有耐药性，但在体外培养时，药物敏感性明显增加。阐明了体内耐药机制。细胞在质膜上表达多种ABC转运蛋白，在体外培养过程中转运蛋白中MRP2的表达消失，加入共轭胆红素后MRP2的表达增加。这些结果强烈提示，当癌细胞在宿主体内生长时，胆红素诱导的MRP2挤出顺铂等抗癌药物，癌细胞对抗癌药物产生耐药性。另一方面，MRP2在患者肿瘤标本中的表达水平差异较大。因此，估计肿瘤活检标本的转运蛋白表达水平可能对癌症化疗非常有用，并成为量身定制的化疗方案。

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.