Presentation Selection of effective adjuvant therapy agent for colon cancer with a novel 3D culture screening system: Evaluation with molecular imaging technique

Yoshii, Yukie  ,  Furukawa, Takako  ,  Aoyama, Hironori  ,  Adachi, Naoya  ,  Ming-Rong, Zhang  ,  Wakizaka, Hidekatsu  ,  Fujibayashi, Yasuhisa  ,  Saga, Tsuneo

Colon cancer is one of the leading causes of cancer death worldwide. For this cancer, adjuvant chemotherapy after surgery of the primary treatment is suggested to be beneficial to eradicate invisible small tumors; however the effective drug remains to be determined. Recently, we reported a novel drug screening system using nanoimprinting 3D culture to make multicellular spheroids that simulates in vivo conditions, thereby predicting effective drugs in vivo (Yoshii et al. Biomaterials 2015). Here, we performed drug screening using this system to find out the effective drug for adjuvant therapy against colon cancer and evaluated the therapeutic effect in vivo with molecular imaging technique. Methods: A human colon cancer HCT116 cells with a stable expression of red fluorescent protein (HCT116-RFP) were cultured in 3D using nano-culture plates (SCIVAX) and in vitro drug screening was performed with 8 clinically-used antitumor agents for colon cancer (bevacizumab, capecitabine, cetuximab, 5-fluorouracil (5-FU), irinotecan, oxaliplatin, panitumumab, and regorafenib). In vivo treatment study was performed with mice bearing HCT116-RFP intraperitoneally disseminated tumors and the therapeutic effect was evaluated with FLT-PET and fluorescent imaging. Results: From 3D screening, regorafenib was the most effective drug. FLT-PET and fluorescent imaging showed that regorafenib substantially inhibited tumor growth, compared to control and treatment group with 5-FU that was not effective both in 3D screening and in vivo. Conclusions: We found that regorafenib was an effective drug against disseminated HCT116-RFP small tumors through 3D screening. This 3D system would be useful to develop effective adjuvant therapy agents for colon cancer.
The International Chemical Congress of Pacific Basin Socie 2015

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