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Updated: Sep 24, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
In vitro antitumor activity of rebeccamycin analog (NSC# 655649) against pediatric solid tumors
S Weitman1, R Moore, H Barrera
1Department of Pediatrics, University of Texas Health Science Center, San Antonio, Texas 78284-7810, USA.
Purpose:
This study determined the in vitro antitumor activity of a rebeccamycin analog (NSC# 655649) using tetrazolium/formazan (MTT) and clonogenic assays against established pediatric cell lines and solid tumor specimens obtained from children.
Materials And Methods:
Tumor cells from 14 established cell lines and 20 patient specimens were exposed in vitro for 1 hour to NSC# 655649 at concentrations ranging from 0.015 to 15.0 microM. The cytotoxicity (IC50) of this agent against established cell lines was determined using both the MTT (cytotoxic) and clonogenic/soft agar cloning (cytostatic) assays. Tumor specimens from children undergoing biopsy or surgical resection were also evaluated in vitro against NSC# 655649 using the clonogenic assay. For studies using patient specimens, antitumor activity was measured by comparing the number of tumor colonies from NSC# 655649-treated cells with those from solvent-treated controls.
Results:
These studies showed that the mean IC50S using the MTT and clonogenic assays using established solid tumor cell lines were 0.94 and 0.51 microM, respectively. In general, for cell lines tested using both types of assays, the clonogenic assay resulted in a smaller IC50. The overall in vitro responses (< or = 50% survival compared to controls) using patient tumor specimens and the clonogenic assay were 35% (1.5 microM), 60% (7.5 microM), and 80% (15.0 microM). Of the 9 patients with neuroblastoma, responses to NSC# 655649 were seen in 33% (1.5 microM), 58% (7.5 microM), and 92% (15.0 microM) of the specimens. Prior chemotherapy did not appear to adversely affect in vitro responses.
Conclusions:
NSC# 655649 appears to have broad antitumor activity in vitro against pediatric malignancies at drug concentrations achieved during adult phase I clinical trials. These studies support the further development of NSC# 655649 for solid tumors in children.
Insights
A rebeccamycin analog (NSC# 655649) demonstrated significant in vitro antitumor activity against pediatric solid tumors. This agent shows promise for further development in treating childhood cancers.
Area of Science:
- Oncology
- Pharmacology
- Pediatric Medicine
Background:
- Pediatric solid tumors represent a significant challenge in cancer treatment.
- Novel therapeutic agents are crucial for improving outcomes in pediatric oncology.
Purpose of the Study:
- To evaluate the in vitro antitumor activity of a rebeccamycin analog, NSC# 655649.
- To assess the efficacy of NSC# 655649 against established pediatric cancer cell lines and primary tumor specimens.
Main Methods:
- Utilized tetrazolium/formazan (MTT) and clonogenic assays to determine cytotoxicity (IC50).
- Exposed 14 established pediatric cell lines and 20 patient tumor specimens to NSC# 655649 in vitro.
- Assessed antitumor activity by comparing colony formation in treated versus control groups.
Main Results:
- NSC# 655649 exhibited mean IC50 values of 0.94 microM (MTT) and 0.51 microM (clonogenic assay) against cell lines.
- In patient specimens, significant responses were observed, with up to 80% tumor cell inhibition at 15.0 microM.
- Neuroblastoma specimens showed high sensitivity, with up to 92% response at 15.0 microM.
Conclusions:
- NSC# 655649 displays broad in vitro antitumor activity against pediatric malignancies.
- Drug concentrations achieved in adult Phase I trials suggest potential clinical relevance.
- Further development of NSC# 655649 for pediatric solid tumors is warranted.
