Geijigajakyak decoction inhibits the motility and tumorigenesis of colorectal cancer cells

Abstract

BackgroundRecent studies report that inflammatory diseases of the large intestine are associated with colorectal cancer. Geijigajakyak Decoction (GJD) has antispasmodic and anti-inflammatory effects on the gastrointestinal tract. Thus, in light of the connection between chronic bowel inflammation and colorectal cancer (CRC), we asked whether GJD inhibits colorectal tumorigenesis.MethodsThe effects of GJD on the viability and proliferation of CRC cells were evaluated using MTT and BrdU assays, respectively. The motility of CRC cells was examined by a Transwell migration/invasion assay and immunoblot analysis was used to examine the signaling pathways associated with migration. A syngeneic Balb/c mice allograft model, in which CT26 cells were injected into the dorsum, was used to evaluate the anti-tumor effects of GJD in vivo.ResultsGJD had no cytotoxic effects against HCT116 CRC cells, although it did inhibit their proliferation. GJD inhibited the migration of HCT116 cells, and suppressed the invasion of HCT116, Caco2, and CSC221 CRC cells. In addition, GJD downregulated the expression of p-JNK and p-p38 MAPK, which are downstream signaling molecules associated with invasiveness. Furthermore, oral administration of GJD (333 mg/kg, twice a day) inhibited tumor growth in a mouse xenograft model.ConclusionsGJD inhibited the motility of human CRC cells and suppressed tumorigenesis in a mouse model. These results suggest that GJD warrants further study as a potential adjuvant anti-cancer therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1281-z) contains supplementary material, which is available to authorized users.

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“…), Da Zao ( Ziziphus jujuba Mill.) HCT-116 – Invasion ↓ ↓: p-JNK, p-p38 MAPK JNK p38 MAPK [ 103 ] Weichang’an (WCA) Tai Zi Shen ( Peseudostellaria heterophylla (Miq. )Pax ex pax et Hoffm.…”

“…QZC could exert a pro-apoptotic effect on HCT-116 cells by activating the MAPK/ERK signaling pathway mediating the upregulation of NAG-1/GDF15. Lee et al [ 103 ] found that the expression of p-JNK and p-p38 MAPK was downregulated in HCT-116 cells after Geijigajakyak decoction (GJD) intervention, suggesting that GJD plays a role in anti-CRC invasion through JNK and p38 MAPK signaling pathways (Fig. 3 ).…”

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“…where a and b are defined as the longest and shortest diameters (in millimeters) of the tumors, respectively. 16 TGI % ð Þ¼…”

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“…Traditional Chinese medicine (TCM) plays an indispensable role in the integrative treatment of advanced CRC and has been widely used in China and other parts of Asia. It has been widely reported that TCM could prolong the survival time and improve the quality of life of patients with CRC by preventing tumorigenesis, suppressing tumor growth, and reducing metastasis and recurrence [13][14][15][16]. Moreover, as an adjunct therapy, TCM could increase the sensitivity and alleviate the side effects of chemotherapy or radiotherapy, improve immunity, lessen the damage induced by conventional treatments, and ameliorate bone marrow suppression [11,[17][18][19][20].…”