Iigo M, Shimamura M, Sagawa K, Tsuda H
Chemotherapy Division, National Cancer Center Research Institute, Tokyo.
Jpn J Cancer Res. 1995 Sep;86(9):867-72. doi: 10.1111/j.1349-7006.1995.tb03098.x.
This study was performed to evaluate the antimetastatic activity of antitumor agents against metastatic colon carcinoma 26 (Co 26Lu), and to investigate their mechanisms of action. Pirarubicin demonstrated the most striking antitumor activity in mice bearing intravenously injected Co 26Lu cells. Etoposide and mitoxantrone also showed marked antitumor activity. Pirarubicin and mitoxantrone also exerted remarkable inhibitory effect on spontaneous lung metastases from subcutaneously implanted Co 26Lu. Pirarubicin showed marked inhibition of both primary tumor growth and lung metastases. Mitoxantrone was effective in preventing lung metastases even at doses that did not exhibit an antitumor effect on the primary tumor. Moreover, mitoxantrone administered two days after intravenous injection of tumor cells obviously reduced the number of lung colonies, while simultaneous injection of the drug did not inhibit colony formation. Mitoxantrone effectively inhibited angiogenesis on the chorioallantoic membrane at doses that did not affect the growth rate of embryos. These results suggest that mitoxantrone, besides its direct antitumor effect on tumor cells, may inhibit lung metastases by inhibiting angiogenesis.
本研究旨在评估抗肿瘤药物对转移性结肠癌26（Co 26Lu）的抗转移活性，并探讨其作用机制。吡柔比星在静脉注射Co 26Lu细胞的小鼠中表现出最显著的抗肿瘤活性。依托泊苷和米托蒽醌也显示出显著的抗肿瘤活性。吡柔比星和米托蒽醌对皮下植入Co 26Lu引起的自发性肺转移也有显著的抑制作用。吡柔比星对原发性肿瘤生长和肺转移均有显著抑制作用。米托蒽醌即使在对原发性肿瘤无抗肿瘤作用的剂量下也能有效预防肺转移。此外，在静脉注射肿瘤细胞两天后给予米托蒽醌明显减少了肺集落的数量，而同时注射该药物则不抑制集落形成。米托蒽醌在不影响胚胎生长速率的剂量下有效抑制了绒膜尿囊膜上的血管生成。这些结果表明，米托蒽醌除了对肿瘤细胞有直接抗肿瘤作用外，还可能通过抑制血管生成来抑制肺转移。
