K-RAS knock down impairs tumor growth of pancreatic models <i>in vivo</i>.

<p>(A) For each xenograft model indicated, tumors were grown subcutaneously in female nude mice and groups of at least 4 mice each were formed once tumors had reached a size of 200–300 mm³. The first group was given normal drinking water, whereas the second was given drinking water containing 2 mg/ml doxycycline and 10% sucrose. Mice were sacrificed after one week of treatment (after 18 days in case of the K-RAS wild type model), and tumors were analyzed by qPCR for K-RAS. K-RAS levels were normalized to ribosomal protein s18. Obtained p-values were as follows: Capan-1 shNT: p = 0.35, Capan-1 sh236: p = 0.011, Panc 10.05 sh236: p = 0.009, AsPC-1 sh236: p = 0.002, L3.3 sh236: p = 0.004, NCI-H1437 sh236: p = 0.007. (B/C) As in (A), except that mice were randomized to groups of at least 6 mice each, with the exception of the Panc 10.05 model, where the group size was n = 4. Treatment was started once tumors had reached a size of 100 mm³, tumor size was followed over time, and mice were sacrificed once tumors of the control group reached a size of 1000 mm³ at most. Statistically significant differences of tumor volumes between groups (*) as well as the area under the curve (AUC/mm³ x treatment days) are indicated. Obtained p-values for AUC at the end of the study were as follows: Capan-1 shNT: p = 0.57, Capan-1 sh236: p = 0.04, Panc 10.05 sh236: p = 0.01, AsPC-1 sh236: p = 0.01, L3.3 sh236: p = 0.0003, NCI-H1437: p = 0.22. The PANC-1 cells could not be grown <i>in vivo</i>, and for this reason this model was only examined <i>in vitro</i>.