Figure 4.

Decitabine inhibits OXPHOS and the growth of ibrutinib-resistant MCL cells

(A) A schematic of ex vivo OMI experiments in Z-138 xenografts.

(B) Representative images of the fluorescence intensity of NAD(P)H and FAD in PBS (control, n = 3) and decitabine-treated mice (n = 3). Scale bar, 25 μm.

(C) Representative images of τ_m of FAD in control and decitabine-treated mice (left) and the quantification of FAD τ_m (right) at the single-cell level (control = 2,544 cells; decitabine = 1,743 cells). Bars represent mean ± SD. Different colors denote separate imaging days. Scale bar, 25μm.

(D) Single-cell quantifications of the lifetime of bound FAD (τ₁) (ps, picosecond), the percentage of bound FAD (α₁), the lifetime of free FAD (τ₂), and the percentage of free FAD (α₂).

(E) Representative of images of the optical redox ratio and the single-cell quantifications of optical redox ratio. Different colors denote separate imaging days. Scale bar, 25 μm. Mann-Whitney U test was used in (C)–(E).

(F) Z138 xenografts, the same as in (A). Red arrows indicate treatment start and end dates. Tumor dimensions were measured with calipers 3 times per week until endpoint, defined as any dimension exceeding 20 mm or mice becoming morbid.

(G) The effect of decitabine in MCL-7 PDXs.

(H) Bioluminescence images of MCL-4 PDX mice (left), growth curves presented as log₁₀ of the average radiance of tumors (ps⁻¹cm⁻²sr⁻¹), with dashed line indicating that all of the mice are euthanized (center), and the probability of survival (right) are shown. Error bars represent mean ± SEM (2-way ANOVA). sr: steradian or square radian.