Figure 4
Figure 4. Ribavirin is active a TH DLBCL patient-derived xenograft (PDX) model. (A) Polysomal profiling of BCL6, BCL2, MYC, and GAPDH (as control) transcripts in OCI-Ly1, DoHH2, and SU-DHL6 cells treated with vehicle (black dotted line) vs ribavirin (RBV). Each profiling is normalized to the respective vehicle represented with a dotted central line. Points localized above and below the line represent polysome fractions enriched and depleted in RBV-treated cells. (B) Total polysomal profiling of DoHH2, OCI-Ly1, and SU-DHL6 cells treated with vehicle (black line) vs ribavirin (red line). (C) Total protein levels in OCI-Ly1 cells treated with vehicle (V) and ribavirin (R). Previously synthesized protein is marked as old and newly synthesized protein is marked as new. Actin was used as control. (D) Protein levels of BCL6, BCL2, MYC, eIF4E, and actin (as control) in SU-DHL6 cells treated with vehicle (V) vs ribavirin (R) for 48 hours. Densitometry analysis is shown on the right for replicates experiments as mean ± SEM conducted in SU-DHL6, OCI-Ly1, and DoHH2 cell lines. (E) In vivo effect of ribavirin (blue dots) vs vehicle (green dots) in the PDX-4 mice. (F-G) Gene Set Enrichment Analysis of decreased transcripts upon ribavirin treatment in PDX-4 mice and eIF4E nuclear targets from RIP-seq experiments. (H) Cytosolic vs nuclear distribution of BCL6, BCL2, MYC, and GAPDH (as control) mRNAs from the PDX-4 after ribavirin treatment of 3 hours or 6 hours. FDR, false discovery rate; NES, normalized enrichment score.

Ribavirin is active a TH DLBCL patient-derived xenograft (PDX) model. (A) Polysomal profiling of BCL6, BCL2, MYC, and GAPDH (as control) transcripts in OCI-Ly1, DoHH2, and SU-DHL6 cells treated with vehicle (black dotted line) vs ribavirin (RBV). Each profiling is normalized to the respective vehicle represented with a dotted central line. Points localized above and below the line represent polysome fractions enriched and depleted in RBV-treated cells. (B) Total polysomal profiling of DoHH2, OCI-Ly1, and SU-DHL6 cells treated with vehicle (black line) vs ribavirin (red line). (C) Total protein levels in OCI-Ly1 cells treated with vehicle (V) and ribavirin (R). Previously synthesized protein is marked as old and newly synthesized protein is marked as new. Actin was used as control. (D) Protein levels of BCL6, BCL2, MYC, eIF4E, and actin (as control) in SU-DHL6 cells treated with vehicle (V) vs ribavirin (R) for 48 hours. Densitometry analysis is shown on the right for replicates experiments as mean ± SEM conducted in SU-DHL6, OCI-Ly1, and DoHH2 cell lines. (E) In vivo effect of ribavirin (blue dots) vs vehicle (green dots) in the PDX-4 mice. (F-G) Gene Set Enrichment Analysis of decreased transcripts upon ribavirin treatment in PDX-4 mice and eIF4E nuclear targets from RIP-seq experiments. (H) Cytosolic vs nuclear distribution of BCL6, BCL2, MYC, and GAPDH (as control) mRNAs from the PDX-4 after ribavirin treatment of 3 hours or 6 hours. FDR, false discovery rate; NES, normalized enrichment score.

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