RT Journal Article
SR Electronic
T1 Raltitrexed as a synergistic hyperthermia chemotherapy drug screened in patient-derived colorectal cancer organoids
JF Cancer Biology and Medicine
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 750
OP 762
DO 10.20892/j.issn.2095-3941.2020.0566
VO 18
IS 3
A1 Zeng, Lisi
A1 Liao, Quanxing
A1 Zhao, Haoran
A1 Jiang, Shengwei
A1 Yang, Xianzi
A1 Tang, Hongsheng
A1 He, Qingjun
A1 Yang, Xiansheng
A1 Fang, Shuxian
A1 He, Jinfu
A1 Cui, Weiwen
A1 Huang, Laiqiang
A1 Ma, Shaohua
A1 Cui, Shuzhong
YR 2021
UL http://www.cancerbiomed.org/content/18/3/750.abstract
AB Objective: Organoids have recently been used as in vitro models to screen chemotherapy drugs in combination with hyperthermia treatment in colorectal cancer. Our research aimed to establish a library of patient-derived colorectal cancer organoids to evaluate synergism between chemotherapy drugs and hyperthermia; validate an index of the hyperthermia chemotherapy sensitization enhancement ratio (HCSER) to identify the chemotherapeutics most enhanced by hyperthermia; and recommend chemotherapy drugs for hyperthermic intraperitoneal treatment.Methods: Organoids were grown from cells extracted from colorectal cancer patient samples or colorectal cancer cell lines. Cells from both sources were encapsulated in 3D Matrigel droplets, which were formulated in microfluidics and phase-transferred into identical cell-laden Matrigel microspheres. The microspheres were seeded in 96-well plates, with each well containing a single microsphere that developed into an organoid after 7 days. The organoids were used to evaluate the efficacy of chemotherapy drugs at both 37 °C as a control and 43 °C for 90 min to examine hyperthermia synergism. Cell viability was counted with 10% CCK8.Results: We successfully established a library of colorectal cancer organoids from 22 patient parental tumors. We examined the hyperthermia synergism of 7 commonly used hyperthermic intraperitoneal chemotherapy drugs. In 11 of the 22 patient organoids, raltitrexed had significant hyperthermia synergism, which was indexed as the highest HCSER score within each patient group.Conclusions: Our results primarily demonstrated the use of patient-derived colorectal cancer organoids as in vitro models to evaluate hyperthermia synergistic chemotherapeutics. We found that hyperthermia enhanced the effect of raltitrexed the most among the common anti-colorectal cancer drugs.