Based on how much I've worked with MDF in general, my instincts tell me that MDF wouldn't last that long. It might
get you started, though. UHMW, HDPE, or maybe even thick phenolic plate would probably do better, and of course aluminum itself would be the best thing short of welded steel channel. Corian would work probably work well too.
Last night I went ahead and purchased the Momus CNC plans ($20), and while it's not a large or heavy duty machine, it definitely has some really interesting aspects. The plans are incredibly well done and very to-the-point. (The Solsylva plans in comparison were more of a doctorate thesis with a lot of theory and not as much practical application as I had hoped.) Stock, the Momus' cutting area is about 16" x 16", and if I do this one as my first machine I'd like to adapt that to 18" x 28" and use a 2.25HP router (Hitachi M12V, Porter-Cable 890-type, etc.) instead of a sub-1HP laminate trimmer router (ie. Bosch Colt, etc.).
There is a guy here on the forum, user "FLB", that used a Momus to cut out a scale VW Beetle floorpan out of aluminum for a Sand Scorcher project. Here's the thread: Aluminum Scorcher Chassis/Desert Build
Video of the thingy doing the jiggy:
And a couple more examples of Momus aluminum milling…
I guess it all comes down to feed rate and the right kind of cutting bit.