Effectiveness of water soluble poly(L-glutamic acid)-camptothecin conjugate against resistant human lung cancer xenografted in nude mice

  • Authors:
    • Y. Zou
    • Q.-P. Wu
    • W. Tansey
    • D. Chow
    • M.-C. Hung
    • C. Charnsangavej
    • S. Wallace
    • C. Li
  • View Affiliations

  • Published online on: February 1, 2001     https://doi.org/10.3892/ijo.18.2.331
  • Pages: 331-336
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Abstract

A camptothecin (CPT) formulation that can be easily administered, is less toxic, and has greater antitumor effect is needed. In this study, a water-soluble CPT derivative was obtained by direct coupling of CPT to poly(L-glutamic acid) (PG) through the C20(S)-hydroxyl group. CPT was released from the resulting conjugate, PG-CPT, in phosphate-buffered saline with a zero-order kinetics in the initial 50 days. The release rates were 0.623% per day, 1.081% per day, and 1.396% per day at pH 5.3, 7.4, and 9.0, respectively. In vitro, PG-CPT was less potent in inhibiting cell growth than was free CPT in all human tumor cell lines tested. However, PG-CPT showed better antitumor activity and tolerability than did CPT in vivo. When H322 human lung tumor cells were inoculated subcutaneously in nude mice, PG-CPT delayed the growth of these well-established tumors with an absolute growth delay of 32 days when given as 4 doses with 4-day intervals between injections at an equivalent CPT dose of 40 mg/kg. When H322 cells were inoculated intratracheally in nude mice, 5 doses of intravenous injection of PG-CPT at an equivalent CPT dose of 10 mg/kg on days 4, 8, 12, 16, and 20 after inoculation significantly prolonged the median survival of treated mice, averaging 1.8-fold that of untreated mice (p=0.01). Increasing the dose of PG-CPT to an equivalent CPT dose of 40 mg/kg per injection administered in 4 doses on days 4, 8, 12, and 16 prolonged the median survival of treated mice by 4-fold (p=0.0008). Significantly, mice with intratracheally inoculated H322 tumors were resistant to both CPT and cisplatin treatments. These studies demonstrated that PG may be used as an effective solubilizing carrier for CPT and that PG-CPT may have potential application in the treatment of lung cancer.

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February 2001
Volume 18 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Zou Y, Wu Q, Tansey W, Chow D, Hung M, Charnsangavej C, Wallace S and Li C: Effectiveness of water soluble poly(L-glutamic acid)-camptothecin conjugate against resistant human lung cancer xenografted in nude mice. Int J Oncol 18: 331-336, 2001.
APA
Zou, Y., Wu, Q., Tansey, W., Chow, D., Hung, M., Charnsangavej, C. ... Li, C. (2001). Effectiveness of water soluble poly(L-glutamic acid)-camptothecin conjugate against resistant human lung cancer xenografted in nude mice. International Journal of Oncology, 18, 331-336. https://doi.org/10.3892/ijo.18.2.331
MLA
Zou, Y., Wu, Q., Tansey, W., Chow, D., Hung, M., Charnsangavej, C., Wallace, S., Li, C."Effectiveness of water soluble poly(L-glutamic acid)-camptothecin conjugate against resistant human lung cancer xenografted in nude mice". International Journal of Oncology 18.2 (2001): 331-336.
Chicago
Zou, Y., Wu, Q., Tansey, W., Chow, D., Hung, M., Charnsangavej, C., Wallace, S., Li, C."Effectiveness of water soluble poly(L-glutamic acid)-camptothecin conjugate against resistant human lung cancer xenografted in nude mice". International Journal of Oncology 18, no. 2 (2001): 331-336. https://doi.org/10.3892/ijo.18.2.331