Combined antitumor effects of a new molecular targeting agent lapatinib with chemotherapeutic agents in poorly differentiated and undifferentiated thyroid cancer cells *
【Subjective】 Poorly differentiated and undifferentiated thyroid cancers are resistant to various therapies. Antitumor activity of a new molecular targeting agent lapatinib（Lap）alone and its combination with chemotherapeutic agents were investigated in poorly differentiated and undifferentiated thyroid cancer cells. 【Materials and Methods】 Three thyroid cancer cell lines（KTC-1 poorly differentiated papillary thyroid cancer cell line, and KTC-2 and KTC-3 undifferentiated thyroid cancer cell lines）established in our laboratory were used. Antitumor activities and effects of Lap and/or chemotherapeutic agents（5-fluorouracil［FU］, doxorubicin［Dox］, paclitaxel［Pac］, SN-38, cisplatin［Cis］, etoposide［Eto］and Cis＋Eto）on the cell cycle progression, induction of apoptosis and expression levels of apoptosis-related factors were investigated. 【Results】 Lap showed dose-dependent antitumor activity（50％ growth inhibitory concentrations:5.0μM for KTC-1 cells, 3.4μM for KTC-2 cells and 3.5μM for KTC-3 cells）and induction of apoptosis in these cell lines. The combined treatment of Lap with SN-38, Cis, Eto or Cis＋Eto resulted in additive antitumor activity in KTC-1 cells. That of Lap with Cis＋Eto leaded to additive antitumor activity in KTC-2 cells. That of Lap with Dox or Pac resulted in additive antitumor activity in KTC-3 cells. The combined treatment of Lap with Cis＋Eto resulted in additive effects on the reduction in survivin protein expression levels and induction of apoptosis in KTC-1 cells. 【Conclusions】 Lap showed antitumor activity associated with induction of apoptosis in poorly differentiated and undifferentiated thyroid cancer cells. Lap occasionally enhanced antitumor activity of cytotoxic chemotherapeutic agents in these cells. These findings suggest that Lap is a promising agent for the treatment of poorly differentiated and undifferentiated thyroid cancers. (Accepted on September ２，2008)
