3‑methylbenzoic Acid

*In Vivo* Experiments {#sec4.3}

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The procedures used to deliver GCFs to Wistar rats were performed on 8-week-old male rats (250--300 g, Envigo). GCF delivery was performed as reported.^[@ref9]^ Briefly, GCFs suspension was prepared and diluted in 1 mL of sterile PBS, injected through I.P. into the right vena cava. Rats were given an intraperitoneal injection of 4 mg/kg etoposide for 4 days, followed by 15 days of etoposide (daily 1.5 mg/kg) injections, and receiving further 3 days of an intraperitoneal injection of 4 mg/kg etoposide daily for 2 consecutive weeks. When animals achieved a 70% tumor inhibition, which was defined as the point of maximum sensitivity to treatment, the rats were subjected to a second protocol of etoposide treatment (14 days of etoposide, and daily 3-days of etoposide + 2 consecutive days of etoposide + vehicle control). After 10 days of etoposide treatment, animals were subjected to an in vivo test to determine if they could tolerate the long-term treatment. Tumor inhibition was assessed by tumor bioluminescence from animals that had received etoposide that were humane sacrificed in a manner similar to that described by Zagdun et al. ([Figure [2](#fig2){ref-type="fig"}](#fig2){ref-type="fig"}).^[@ref42]^

### Cell Cultures and Cell Line Establishment {#sec4.3.1}

The human colorectal cancer cell lines SW480, HCT-8, SW480-KD, HCT-8-KD, SW480-KD cells, HCT-8-HDR cells, SW480/CDDP cells, HCT-8/CDDP cells, and HCT-8-HDR/CDDP cells were selected for analysis. The SW480 cells were kindly provided by Dr. K. Koh, as a gift from Prof. J. W. Hirsch (Harvard University).