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Aim To study the pharmacokinetics of po-lyethylene glycol conjugation on EILDVP peptide in mice by injection through tail vein.Methods KM mice,saturated thyroid gland with compound of NaI, were injected for 1 25 I labeled EILDVP-Tyr-NH2 ,EILD-VP-Cys (mPEG2000-MAL)-Tyr-NH2 and EILDVP-Cys (mPEG20000-MAL)-Tyr-NH2 peptides (1 25 I:5 mL · kg -1 volume 3.441 GBq·L -1 concentration)by tail intravenous,respectively.Blood samples at different time intervals were obtained,blood plasma was separa-ted,and the radioactivity of precipitation after trichloro-acetic acid (TCA)treatment was tested.According to standard curve equation, the plasma concentration curve and pharmocokinetic parameters were depicted by means of 3P97 pharmocokinetics software.Results Concentration range of 3.75 ~480 μg·L -1 of three 1 25 I labled peptides in plasma from mice had good line-ar relationship.Recovery of method was 88.92% ~ 1 06.66%,and RSD <1 0%.The half-life time (T1 /2 ) of EILDVP-Tyr-NH2 peptide modified by mPEG2000 and mPEG20000 ,labled by 1 25 I was 0.43h and 1 .94h,re-spectively,which was 1 .54 times and 6.93 times that of prototype peptide (T1 /2 =0.28h),and the clear-ances (Cl)were 1 .23 times and 24.71 times,respec-tively.The apparent distribution volume (V)values of the three species were small,which might mainly dis-tributed in the plasma.Conclusions Suitable for mo-lecular mass mPEG modified the EILDVP peptides could extend to maintain time in vivo,which could play a positive role in improving efficacy.In the experimen-tal range,EILDVP peptide modified by larger molecu-lar mass of mPEG20000 has better effect.
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BACKGROUND: The invasion of highly metastatic carcinoma cells on reconstituted basement membrane component is considered as a common model for in vitro experimental studies of invasion and metastasis of malignant tumors. It has been reported that synthetic peptide influences some tumor cells. However, the effect of synthetic peptide on highly metastatic human lung giant-cell carcinoma cell(PG) has been rarely studied.OBJECTIVE: To study the effects of synthetic peptide RGD, YIGSR and their derivatives on invasive ability of PG in vitro.DESIGN: A completely randomized controlled trial was conducted.SETTING and MATERIALS: The human lung highly metastatic tumor and NIH3T3 cell line were both supplied by the Department of Pathology of Beijing Medical University. The synthetic peptides were provided by the Synthetic Laboratory of the Institute of Materia Medica of the Chinese Academy of Medical Sciences and Chengde Medical College. Transwell invasion chamber was purchased from Costor Company. The whole experiment was conducted at the Department of Biochemistry of Chengde Medical College.INTERVENTIONS: NIH3T3 cell line was used to prepare chemotactic factor. PG cells were seeded in Transwell invasion chamber. Under the effect of chemotactic factor, the effects of synthetic peptides on PG invasive ability were examined.MAIN OUTCOME MEASURES: PG cell number of passing through the reconstituted basement membrane was used as an index to evaluate the invasive ability of tumor cells.RESULTS: An appropriate number of PG cells were cultured for 10 hours with chemotactic factor, and the number ofinvasive cells reached a number range that can be applied to statistical analysis(50 to 100 invasive cells). After 100 mg/L of synthetic peptides RGD, YIGSR were incubated for 48 hours with PG cells,the rate of inhibition on invasive ability was 53.63% and 36.86% respectively, and 0% and 6.48% respectively after incubation for 10 hours.CONCLUSION: The PG cells were the proper cells for in vitro experimental studies of invasive ability of cancer cells for the purpose of screening of anti-tumor medicine. RGD and Juncha/Zacha-peptide YIGSR showed a strong activity in inhibiting tumor invasion and a potential value in prevention and treatment of malignant tumor development.