Table 4.
Summary of the EC50 values and viability reductions achieved for the lung cancer (LC) (IMR90 is benign) cell lines treated with the DNA methyl-transferase inhibitors (DNMTIs) decitabine and zebularine. For H1975, HCC827, HCC4006, and H1437, additional EC50 values for tyrosine kinase inhibitor (TKI) treatments with gefitinib and erlotinib are shown. Student’s t-test gave no statistically significant p-value comparing viability reduction and EC50 values for female vs. male cancerous cell lines (decitabine: p = 0.22, zebularine: p = 0.41). A statistically significant difference between the decitabine EC50 values of mut versus wt cell lines was found (p = 0.01). No statistical significance was reached for zebularine (p = 0.12) (Figure 4). A Mann–Whitney U test for the EC50 values of cancerous cell lines with methylations scores >8 compared to cancerous cell lines with methylation scores <8 showed no statistically significant difference for neither decitabine (p = 1.0) nor zebularine (p = 0.39).
| Cell Line | Mutational Status | Methylation Score | EC50 Decitabine [µM] | EC50 Zebularine [µM] | Viability Reduction Decitabine | Viability Reduction Zebularine | EC50 Gefitinib | EC50 Erlotinib |
|---|---|---|---|---|---|---|---|---|
| H1975 | EGFR mut | 9 | 24.42 | 97.68 | 60% | 42% | >10 µM | >10 µM |
| H1993 | EGFR amp | 9 | 83.5 | 493.8 | 36% | 40% | ||
| HCC827 | EGFR mut | 10 | 63.72 | 267.9 | 37% | 62% | 2.39 nM | 1.29 nM |
| H2347 | KRAS mut | 10 | 46.85 | 378.1 | 34% | 21% | ||
| IMR90 | wt | 7 | 146.8 | 230.3 | 58% | 54% | ||
| H4006 | EGFR mut | 6 | 33 | 117.9 | 36% | 77% | 276 nM | 259 nM |
| H647 | KRAS mut | 6 | 63.43 | 184.3 | 55% | 33% | ||
| H1437 | wt | 6 | 132.6 | 275.6 | 41% | 21% | >10 µM | >10 µM |
| H2087 | wt | 9 | 187 | 319.9 | 32% | 39% | ||
| average female LC a | 54.6 | 309.4 | 42% | 41% | ||||
| average male LC b | 104.0 | 224.4 | 41% | 43% | ||||
| average mutated LC c | 46.3 | 209.2 | 44% | 47% | ||||
| average wildtype LC d | 134.4 | 363.1 | 36% | 33% | ||||
| average < 8 methylation LC e | 76.3 | 192.6 | 44% | 44% | ||||
| average > 8 methylation LC f | 81.1 | 311.5 | 40% | 41% | ||||
a included are cancerous female cell lines (H1975, H1993, HCC827, H2347) (n = 4). b included are cancerous male cell lines (H4006, H647, H1437, H2087) (n = 4). c included are EGFR/KRAS mutated cancerous cell lines (H1975, HCC827, H2347, H4006, H647) (n = 5). d included are EGFR/KRAS wildtype cancerous cell lines (H1993, H1437, H2087) (n = 3). e included are cancerous cell lines with methylation scores < 8 (H4006, H647, H1437) (n = 3). f included are cancerous cell lines with methylation scores > 8 (H1975, H1993, HCC827, H2347, H2087) (n = 5).