After Replenishing Mechanism Of Prescription Treatment Of Bone Metastases Of Different Return

Background:Traditional Chinese Medicine(TCM) plays an important role in mediating OPG-RANKL-RANK system, the SDF-1/CXCR4axis and the function of NK cell, especially the expression of the active molecule on its surface and differentiation of Th17cells and Treg cells, which are relevant with bone metastasis. It was reported that the efficacy varied and was selected among different channel tropism tonic formulas.Objective:To access and compare the efficacy of different channel tropism tonic formulas in rats with bone metastasis. This study was aimed to investigate the theory of channel tropism based on the role of OPG-RANKL-RANK system, the SDF-1/CXCR4axis and tumor microenvironments in mediating bone metastasis.Methods:A rat model of cancer-induced bone pain using the MRMT-1cell line injected into the tibia was established to investigate the efficacy of different channel tropism tonic formulas on osteoclast activity and bone mineral density. Sprague-Dawley rats receiving intra-tibial injections of syngeneic MRMT-1rat mammary gland carcinoma cells were randomly divided into5groups:sham group, tumor group and3herbal medicine groups (kidney channel, lung channel, liver channel). The development of the bone tumor and structural damage to the bone was monitored on day21by radiological analysis and quantitative measurement of bone mineral density (BMD) and bone mineral content (BMC). Formalin-fixed, paraffin-embedded (FFPE) specimens of the tibial bone were processed for the HE stain and immunohistochemistry to observe the bone pathological changes, count HE stained osteoclasts and semi-quantitatively measure expressions of osteoprotegerin (OPG), receptor activator of nuclear factor-KB ligand(RANKL) and CXC chemokine receptors(CXCR4). The expression of NKG2D of NK cells, Th17cells and Treg cells were processed through flow cytometry(FCM) test.Results:Inoculation of syngeneic MRMT-1mammary tumor cells into one tibia of female rats produced tumor growth within the bone associated with a reduction in bone mineral density (BMD) and bone mineral content (BMC), severe radiological signs of bone destruction. BMD and BMC were preserved and a dramatic reduction of HE phosphatase-positive polykaryocytes (osteoclasts) was observed in Kidney channel group. The expression of OPG showed superior IOD with kidney channel group relative to sham group. The expression of both RANKL and CXCR4were markedly lowered. However it did not remain statistically significant in flow cytometry(FCM) test.Conclusion:Kidney channel formula showed superior anti-metastatic and bone preserving therapeutic effects. It was probably relevant with the role of the SDF/CXCR4axis by increasing the adhesion capability of cancer cells and activity of signaling pathway, as well as mediating OPG-RANKL-RANK system, but not the function of tumor microenvironments.