| BackgroundAccording to the latest report of Parkin and the global statistical report issued by World Health Organization, the annual morbidity of stomach cancer is about 18/10,000,000, declining from the second place to the fourth place. However, the mortality of stomach cancer ranks only second to that of lung cancer. In recent years, about 800,000 more people have got stomach cancer and over 630,000 people died from it. The morbidity and mortality of stomach cancer vary greatly in accordance with geographic differences. As a most commonly-seen malignant tumor, stomach cancer ranks first in its morbidity and mortality among the malignant gastrointestinal tumors. In terms of cause of death, data collected by the information statistics center of Ministry of Health indicate that stomach cancer ranks the third among all malignant tumors. The male/female ratio in the morbidity of stomach cancer is 2/1, and people over 50 years old are more susceptible to it.Nowadays the age of onset tends to be younger, and the morbidity has increased among young and middle-aged people over 30. Stomach cancer is still a serious disease severely impairing people's health in our country. The attack of it is determined by the concurrent external environmental factors and internal physical factors. The former includes direct contract of some cancerogenicsubstances and bad living habits(improper diet, smoking, etc.), while the latter includes the inactivation of cancer suppressor genes and the mutation of proto-oncogenes which induces incontrollable growth regulation of the cells and thus tumor forms. The main therapy for the stomach cancer at early stage is surgery accompanied with neoadjuvant chemotherapy or radiotherapy. Since the stomach cancer at its early stage is difficult to know, it is already the middle and advanced stage or even distant metastasis exists when diagnosed. The distant metastasis makes impossible radical excision of the stomach cancer tissues, for which reason the therapeutic effect on stomach cancer at its late stage is poor and so is the prognosis.Artemisinin is the active ingredient extracted from the leaves and buds of the Artemisia annua(belonging to composite family of traditional Chinese medicine). It contains sesquiterpene lactones of internal peroxide group and is commonly used to treat malaria fever with high efficiency but few toxic and side effects. In recent years, there are increasing researches on artemisinin and its derivatives in antitumor mechanism. Artemisinin and its derivatives can selectively kill the tumor cells, inhibit tumor growth and effectively induce apoptosis of tumor cells. In particular, its derivative dihydro artemisinin(aka dihydroartemisinin) has certain inhibition effect on a variety of tumors and synergistic effect when combined with multiple traditional antitumor drugs. In addition, it also has the effect of inhibiting the formation of tumor angiogenesis as well as the invasion and metastasis of tumor cells.There is a close relationship between the lymphatic microvessel density(LMVD) and the lymph-vessel formation in tumor tissues. Within the tumor, the lymph node tissue can induce the lymph-microvessel formation, so the number of lymph-vessel in the tumor tissues is greatly higher than that in normal tissues. The cancer cells can enter the lymphatic system through the newly-formed lymph-vessel wall, thus leading to cancer metastasis. In the stomach tissues, the count of LMVD in area of lymphatic metastasis is higher than the area without lymphatic metastasis, while there was no significant difference in the counts of LMVD between the stomach tissues without local lymphatic metastasis and benign lesion tissues, so the lymph-microvessel density is an important criterion to detect the cancerous lymphatic metastasis.VEGFR-3(Vascular endothelial growth factor receptor-3) is a transmembrane tyrosine kinase receptor cloned by human leukemic cell lines and human placenta, mainly located in the cell membrane and with the molecular weight of 150 kDa, which is the first-discovered specific markerfound in the lymphatic endothelium. In the lymphatic endothelial cells, it exerts mediating,proliferating and migrating effect and is a key factor of the lymphangiogenesis. VEGFR-3, as the specific receptor of vascular endothelial growth factor-C(VEGF-C), is closely associated with the lymph-vessel formation. By combining with VEGF-C, it induces the proliferation of the endothelial cells, promotes the extension of the lymphatic vessels and the development of the lymphatic sinus, and accelerates the cancerous metastasis.LYVE-1( lymphatic vessel endothelial hyaluronan receptor-1) is a new lymphatic endothelial hyaluronan receptor distributed in the internal and external cavity-surface. It and CD44 are the same homologues. Its main function is to specifically combine the lysotype hyaluronan and fixed-type hyaluronan in the extracellular matrix components, and then transfer the hyaluronate from the tissues to the lymphatic fluid. The high expression of LYVE-1 is closely related with the lymphatic metastasis. LYVE-1 can express in the normal tissues and the endothelial cells of the capillaries in cancer tissues but cannot express in the capillaries and tumor cells. Therefore, LYVE-1 is a kind of lymphatic specific marker, the expression of which is bound up with the lymphatic metastasis.ObjectiveTo study the effect of Dihydroartemisinin(DHA) on transplanted tumor under the skin of nude mice of human gastric cancer cell line SGC?7901 and the formation of lymphatic vessels in vivo.Methods and Methodshuman gastric cancer cell line SGC?7901 was transplanted to subcutane of nude mice to establish the sample and then randomly divided into three groups: saline group, 5?Fu group(20mg/kg), experimental group(DHA100mg/kg), each of group continuously received gavage for15 days in nude mice, once a day, and the nude mice were sacrificed within 24 hours after the drug withdrawal. The volume of tumor, the weight of tumor, the tumor inhibition rate, the anti?tumor rate and the micro lymphatic vessel density of the positive expression on VEGFR?3and LYVE?1 in each group were compared and analyzed.ResultsThe tumor volume of DHA group and 5?Fu group were as follows:(1521.3±346.8mm3),(1638.7±398.6mm3), the tumor inhibition rate as follows:41.8%, 42.3%, the anti?tumor rate as follows:(24.8±3.29)%,(26.8±3.75)%,DHA group and 5?Fu group were significantly lower than that in normal saline group(P<0.01), the micro lymphatic vessel density of DHA group and 5?Fu group of two methods(VEGFR?3 and LYVE?1) as follows:( 13.62±2.89,13.56±2.55) and( 12.86±2.15,12.74±2.21), Compared with the saline group there were the statistically differences(P<0.01).ConclusionDihydroartemisinin(DHA) can inhibit the growth of the tumor under the skin of nude mice of human gastric cancer cell line SGC?7901 in vivo, which can reduce the density of micro lymphatic vessels, The formation of lymphatic vessels is obviously inhibited, which can block the way of the lymphatic metastasis of tumor cells. |
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