Lung cancer xenografts in SDR™ & SRG™ SCID rats

 

Oncogenic mutations in KRAS gene are found in >25% of lung adenocarcinomas, the major histologic subtype of non-small cell lung cancer (NSCLC). KRAS encodes for a GTP-binding protein in the RAS signaling pathway that is involved in apoptosis, differentiation, proliferation and other cellular processes. The H358 non-small cell lung cancer (NSCLC) cell line harbors a heterozygous missense KRAS mutation at codon 12 leading to constitutive activation of the growth-promoting RAS signaling pathway. shRNA-mediated knockdown of mutant KRAS expression inhibits cell proliferation in H358 but does not alter the non-KRAS mutant NSCLC cell line, H1299 (1).  KRAS mutants are relevant targets for NSCLC drug development and improved in vivo xenograft efficacy models using H358 may be valuable for preclinical studies.

 

The SDR SCID rat, which is a Rag2 knockout deficient in B- and T-cells, demonstrated excellent tumor growth kinetics and engraftment rate for the H358 cell line.

 

When the NSCLC H358 cell line harboring a KRAS mutant was implanted into the SDR rat subcutaneously; the tumor growth was faster and more consistent than what has previously been reported in nude, SCID and NSG mouse models. The H358 tumors grew much faster at all three different cell numbers (1,5,10 x106) in SDR rats than SCID mice.

 

Enhanced survival of NSCLC cell line H358 and tumor kinetics in the SDR rat compared to Nude mice and SCID mice (NSG mice)

H358 cancer cells growth in the SDR™ rat compared to the nude (nu/nu) and NSG™ mice. H358 cancer cells were transplanted subcutaneously in the SDR™ rat. Three groups of 6 rats received 1e6, 5e6, or 10e6 cells in 5mg/ml Geltrex®. Growth rate was directly proportional to the amount of cells transplanted. These data are displayed in conjunction with data from the lab of Dr. Goutham Narla showing tumor growth kinetics of the H358 cell line in Nude and NSG™ mice, both of which were transplanted with 10e6 cells subcutaneously.

 

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References

  1. Sunaga et al. (2011) Knockdown of Oncogenic KRAS in Non-Small Cell Lung Cancers Suppresses Tumor Growth and Sensitizes Tumor Cells to Targeted Therapy. Mol Cancer Ther. 10(2): 336–346 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061393/