Gefitinib is a new molecular targeted antitumor drug and recently used widely in lung cancer treatment in China. But when used for an average ten-month period, patient show resistance to gefitinib and this resistance ...Gefitinib is a new molecular targeted antitumor drug and recently used widely in lung cancer treatment in China. But when used for an average ten-month period, patient show resistance to gefitinib and this resistance limit its con- tinued use. Low-molecular-weight heparin （LMWH） has potent inhibitory action on experimental metastasis. In present study, we are trying to find whether LMWH combined with gefitinib could sensitize its antitumor effects and potential relieve its resistance phenomenon in fifo and in vitro. Enoxaparin （one kind of LMWH） combined with gefitinib inhibited the growth of xenografl A549-1uc-C5 tumors in nude mice and reduced lung colony formation compared with gefitinib alone.展开更多
Chemotherapy agents have been widely used for cancer treatment,while the insolubility,instability and toxicity seriously restrict their efficacy.Thus,prodrug strategy was devised.Since some prodrugs are still with poo...Chemotherapy agents have been widely used for cancer treatment,while the insolubility,instability and toxicity seriously restrict their efficacy.Thus,prodrug strategy was devised.Since some prodrugs are still with poor solubility or stability,a synergy strategy is needed to enhance their efficacy.Gemcitabine(GEM)is a prescribed anticancer drug,however,the rapid clearance,growing resistance and serious side effects limit its clinical efficacy.Conjugating GEM with D-a-tocopherol succinate(TOS)is an effective solution,while the GEM-TOS(GT)is unstable in aqueous solution.D-a-Tocopherol polyethylene glycol succinate(TPGS)has been used to enhance the stability,but GT stabilized by TPGS(GTT)has limited effect on tumor metastases.Tumor metastases lead to high mortality in patients suffering from cancers.In order to further achieve antimetastatic effect,an amphiphilic polymer(LT)was synthesized by connecting low-molecular-weight heparin(LMWH)with TOS,and eventually obtained desired selfdelivery micellar NPs(GLT)by co-assembly GT with LT.The GLT not only possessed excellent stability,but also inhibited the metastases by acting on different phases of the metastatic cascade.The hydrophobic TOS inhibited the secretion of matrix metalloproteinase-9(MMP-9),the hydrophilic LMWH inhibited the interaction between tumor cells and platelets.As a result,GLT reduced tumor cells entering the blood and implanting at the distant organs,leading to a much more excellent inhibitory effect on the lung metastasis than GEM and GTT.展开更多
文摘Gefitinib is a new molecular targeted antitumor drug and recently used widely in lung cancer treatment in China. But when used for an average ten-month period, patient show resistance to gefitinib and this resistance limit its con- tinued use. Low-molecular-weight heparin （LMWH） has potent inhibitory action on experimental metastasis. In present study, we are trying to find whether LMWH combined with gefitinib could sensitize its antitumor effects and potential relieve its resistance phenomenon in fifo and in vitro. Enoxaparin （one kind of LMWH） combined with gefitinib inhibited the growth of xenografl A549-1uc-C5 tumors in nude mice and reduced lung colony formation compared with gefitinib alone.
基金supported by Major Projects of the National Natural Science Foundation of China(81690261)Sichuan Science and Technology Program(2018RZ0136,China)
文摘Chemotherapy agents have been widely used for cancer treatment,while the insolubility,instability and toxicity seriously restrict their efficacy.Thus,prodrug strategy was devised.Since some prodrugs are still with poor solubility or stability,a synergy strategy is needed to enhance their efficacy.Gemcitabine(GEM)is a prescribed anticancer drug,however,the rapid clearance,growing resistance and serious side effects limit its clinical efficacy.Conjugating GEM with D-a-tocopherol succinate(TOS)is an effective solution,while the GEM-TOS(GT)is unstable in aqueous solution.D-a-Tocopherol polyethylene glycol succinate(TPGS)has been used to enhance the stability,but GT stabilized by TPGS(GTT)has limited effect on tumor metastases.Tumor metastases lead to high mortality in patients suffering from cancers.In order to further achieve antimetastatic effect,an amphiphilic polymer(LT)was synthesized by connecting low-molecular-weight heparin(LMWH)with TOS,and eventually obtained desired selfdelivery micellar NPs(GLT)by co-assembly GT with LT.The GLT not only possessed excellent stability,but also inhibited the metastases by acting on different phases of the metastatic cascade.The hydrophobic TOS inhibited the secretion of matrix metalloproteinase-9(MMP-9),the hydrophilic LMWH inhibited the interaction between tumor cells and platelets.As a result,GLT reduced tumor cells entering the blood and implanting at the distant organs,leading to a much more excellent inhibitory effect on the lung metastasis than GEM and GTT.
