Inhibitory effects of Chanling Gao on the proliferation and liver metastasis of transplanted colorectal cancer in nude mice

Abstract

This study aimed to explore the efficacy and mechanism of Chanling Gao (CLG), a compound Chinese medicine, on colorectal cancer (CRC). A model of transplanted CRC was established in nude mice. The mice were treated 7 days after CRC transplantation with either Capecitabine or CLG for 3 weeks. On the 28th day after the operation, CRC growth and liver metastasis were assessed by morphology, the changes in the expression of HIF-1α (hypoxia inducible factor-1α), stromal cell–derived factor-1 alpha (SDF-1α), CXCR4 (C-X-C chemokine receptor type 4), PI3K, and Akt in the transplanted tumor and SDF-1α and CXCR4 in the liver were detected by Western blot and immunohistochemistry. The protein contents of vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and collagen IV in the serum and transplanted tumor and SDF-1α and CXCR4 in liver tissues were detected by enzyme-linked immunosorbent assay. In the Capecitabine and high dose CLG groups, the growth and liver metastasis of CRC were significantly inhibited, the protein levels of HIF-1α, SDF-1α, CXCR4, MMP-2, VEGF, PI3K, Akt, P-PI3K and P-Akt in the transplanted tumor were lower, while the content of collagen IV in the transplanted tumor was higher, than in Model group. A high dose of CLG inhibited the growth of transplanted tumor and liver metastasis of CRC in nude mice, probably by inhibiting the HIF-1α/SDF-1α-CXCR4/PI3K-Akt signaling pathway reducing the synthesis and release of VEGF and degradation of collagen IV.

Chanling Gao Attenuates Bone Cancer Pain in Rats by the IKKβ/NF-κB Signaling Pathway

“…Modern pharmacological research suggests that the active constituents of the main components of CLG, such as Chan Pi (Toad Skin), Wei Ling Xian (Clematis chinensis), Ge Gen (Radix Puerariae), Chuan Xiong (Ligusticum chuanxiong Hort), and E Zhu(Curcuma aeruginosa Roxb) exhibit anti-tumor effects that reduce the side effects of chemotherapy and improve immunity (Cao et al, 2015;Lee et al, 2015;Zhang et al, 2018;Hao et al, 2019;Zhan et al, 2020). Our previous study demonstrated that the clinical application of CLG (Huang et al, 2016;Yang et al, 2016;Yang et al, 2019) exhibited a certain relief effect in patients with cancer pain and a significant effect on a colorectal cancer nude mouse model. The HPLC (Supplementary Material: Figure 1, Tables 1 and 2) analysis of CLG indicated (Figure 1A) that this extract mainly contained bufogenins [bufalin (0.47 mg/ml), resibufogenin (0.49 mg/ml), telocinobufagin (0.32 mg/ml), gamabufotalin (0.28 mg/ml), arenobufagin (0.36 mg/ml)] (Figures 1a-e), flavonoids [scutellarin (0.26 mg/ml), apigenin (0.65 mg/ml), kaempferol-7-O-b-D-glucopyranoside (0.41 mg/ml), calycosin (1.37 mg/ml), formononetin (0.44 mg/ml), and nobiletin (0.72 mg/ml)] (Figures 1f-k), alkaloids [ammothamnine (0.36 mg/ml) and magnoflorine (0.98 mg/ml)] (Figures 1l, m) as well as other ingredients, such as emodin (0.39 mg/ml), adenosine (0.56 mg/ ml), 9-Oxo-10(E),12(E)-octadecadienoic acid (0.18 mg/ml), cryptotanshinone (0.55 mg/ml), and diosgenin (0.58 mg/ml) (Figures 1n-r).…”

Chanling Gao suppresses colorectal cancer via PI3K/Akt/mTOR pathway modulation and enhances quality of survival

“…Its effect mechanism was probably related to the inhibition of SDF-1a, CXCR4, and other protein expression. 22 Furthermore, we also proved that CLG had a significant analgesic impact on Walker 256 breast cancer cells in a rat model of cancer pain, and the HPLC analysis of CLG revealed its primary constituents.…”

Therapeutic Effect of Curcumol on Chronic Atrophic Gastritis (CAG) and Gastric Cancer Is Achieved by Downregulating SDF-1α/CXCR4/VEGF Expression

“…Relevant studies have pointed out that the activation of SDF-1 α /CXCR4 axis in either human breast cancer cell lines or prostate cancer cell lines promotes VEGF secretion to participate in tumor angiogenesis [ 14 , 15 ]. In addition, it has been reported that peritoneal metastasis in gastric cancer proves to be related to the interaction between VEGF, CXCR4, and CXCL12.…”