腹膜轉移（Peritoneal Carcinomatosis, PC）為癌症末期疾病，成因是腹腔周遭器官癌症，如大腸直腸癌、胃癌、卵巢癌等，其癌細胞自器官脫落至腹腔中，導致癌細胞附著於腹膜且生長為新的腫瘤，其治療困難且嚴重影響患者生活品質。近年來，腹腔熱化療搭配細胞減積手術獲得關注。先以細胞減積手術切除肉眼可見腫瘤，再將加熱至42~43℃的化療藥物灌流至腹腔中，對腫瘤及游離的癌細胞進行毒殺，由於癌細胞對熱的耐受性較低，因此臨床上具有良好的治療效果。不過藥物選擇通常依據外科醫生治療經驗判斷，但患者間存在個體差異且腹膜轉移源頭不同，故經驗法則不一定適用。本研究設計一系統化的藥物篩選晶片，透過流道的幾何設計，以產生不同藥物組合與不同細胞比例的共培養細胞球體，且分別在37℃與43℃對不同細胞比例球體進行藥物灌流治療，由實驗結果可知，加熱對於藥物治療有加乘效果，透過螢光共定位分析，纖維母細胞比例越高之組別，癌細胞死亡程度較低，推測纖維母細胞對癌細胞有保護及抗藥性之效果，並且發現Cisplatin+ Docetaxel對癌細胞有最良好的毒殺效果。透過此設計模擬不同情況之腫瘤微環境，使篩選結果更貼近體內真實情況，期望透過此晶片提供一可靠的藥篩平台，成為醫生藥物組合治療參考。
關鍵字：微流體晶片、腹膜轉移、腹腔溫熱化療、藥物篩選平台、多細胞腫瘤球體共培養

Peritoneal Carcinomatosis (PC) is terminal cancer caused by cancer in the organs near the abdomen, such as colorectal cancer, gastric cancer, ovarian cancer, etc. PC severely affects the patient's quality of life. In recent years, Hyperthermic Intraperitoneal Chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) has attracted attention to treat peritoneal metastasis. First, the tumors visible to the naked eye are removed by cytoreductive surgery. Then the chemotherapeutic drugs are heated to 42-43°C and perfused into the abdominal cavity. The abdominal cavity is filled with heavy-dense medications to kill the tumor and cancer cells. Due to the low tolerance of cancer cells to heat, it has an excellent clinical therapeutic effect. However, the choice of drugs and their combination is usually based on the surgeon's treatment experience. In addition, the rules of thumb may not apply due to individual differences and different sources of peritoneal metastases.
In this study, we designed a systematic drug screening chip that uses the design of a specific flow channel geometry to generate different drug combinations and co-cultured spheroids with varying ratios of cells. We treated these spheroids with drug perfusion at 37°C and 43°C, respectively. The experimental results showed that the heated group had a synergistic effect on drug treatment. Through fluorescence colocalization analysis, the higher the proportion of fibroblasts, the lower the degree of cancer cell death. We consider that fibroblasts could have a protective and drug-resistant effect on cancer cells. Moreover, we found that the combination of Cisplatin and Docetaxel showed the best cytotoxic effect on cancer cells.
The in-vivo actual situation is approached through our design of the in-vitro tumor and its microenvironment to apply the in-vitro screening results. This microfluidic chip is aimed to provide a reliable drug screening platform and become a reference for doctors' drug combination treatment.

Keywords: Microfluidics chip, Peritoneal carcinomatosis, Hyperthermic Intraperitoneal Chemotherapy, Drug testing platform, Multicellular tumor spheroids

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